Newborns discriminate utterance-level prosodic contours.

Prosody is the fundamental organizing principle of spoken language, carrying lexical, morphosyntactic, and pragmatic information. It, therefore, provides highly relevant input for language development. Are infants sensitive to this important aspect of spoken language early on? In this study, we asked whether infants are able to discriminate well-formed utterance-level prosodic contours from ill-formed, backward prosodic contours at birth. This deviant prosodic contour was obtained by time-reversing the original one, and super-imposing it on the otherwise intact segmental information. The resulting backward prosodic contour was thus unfamiliar to the infants and ill-formed in French. We used near-infrared spectroscopy (NIRS) in 1-3-day-old French newborns (n = 25) to measure their brain responses to well-formed contours as standards and their backward prosody counterparts as deviants in the frontal, temporal, and parietal areas bilaterally. A cluster-based permutation test revealed greater responses to the Deviant than to the Standard condition in right temporal areas. These results suggest that newborns are already capable of detecting utterance-level prosodic violations at birth, a key ability for breaking into the native language, and that this ability is supported by brain areas similar to those in adults. RESEARCH HIGHLIGHTS: At birth, infants have sophisticated speech perception abilities. Prosody may be particularly important for early language development. We show that newborns are already capable of discriminating utterance-level prosodic contours. This discrimination can be localized to the right hemisphere of the neonate brain.

The neonate brain's sensitivity to repetition-based structure: Specific to speech?

Newborns are able to extract and learn repetition-based regularities from the speech input, that is, they show greater brain activation in the bilateral temporal and left inferior frontal regions to trisyllabic pseudowords of the form AAB (e.g., "babamu") than to random ABC sequences (e.g., "bamuge"). Whether this ability is specific to speech or also applies to other auditory stimuli remains unexplored. To investigate this, we tested whether newborns are sensitive to regularities in musical tones. Neonates listened to AAB and ABC tones sequences, while their brain activity was recorded using functional Near-Infrared Spectroscopy (fNIRS). The paradigm, the frequency of occurrence and the distribution of the tones were identical to those of the syllables used in previous studies with speech. We observed a greater inverted (negative) hemodynamic response to AAB than to ABC sequences in the bilateral temporal and fronto-parietal areas. This inverted response was caused by a decrease in response amplitude, attributed to habituation, over the course of the experiment in the left fronto-temporal region for the ABC condition and in the right fronto-temporal region for both conditions. These findings show that newborns' ability to discriminate AAB from ABC sequences is not specific to speech. However, the neural response to musical tones and spoken language is markedly different. Tones gave rise to habituation, whereas speech was shown to trigger increasing responses over the time course of the study. Relatedly, the repetition regularity gave rise to an inverted hemodynamic response when carried by tones, while it was canonical for speech. Thus, newborns' ability to detect repetition is not speech-specific, but it engages distinct brain mechanisms for speech and music. RESEARCH HIGHLIGHTS: The ability of newborns' to detect repetition-based regularities is not specific to speech, but also extends to other auditory modalities. The brain mechanisms underlying speech and music processing are markedly different.

Newborns modulate their crawling in response to their native language but not another language.

Human newborns can propel themselves to their mother's breast when positioned skin to skin on her abdomen just after birth. For decades, researchers have considered this primitive crawling behavior a spinal reflex, immune to supra spinal control. However, recent research suggests that neonatal crawling is already responsive to visual and olfactory stimuli processed at a supra spinal level. Here we report that a few hours post birth, French newborns can also modulate their crawling in response to their native language - a source of information that is processed supra-spinally. The crawling patterns of 23 French-born newborns were recorded on video and via an infrared motion capture system during two randomly ordered 2-min trials. The newborns were secured on a mini skateboard to facilitate arm and leg movements during their crawling propulsion. They heard a repetitive sequence of the same sentences either in French, their native language, or in English, a rhythmically different and hence discriminable unfamiliar language, on each trial. In French, compared to English, crawling was enhanced, with significantly more arm and leg steps and significantly more and larger trunk rotations in the cephalo-caudal axis. Moreover, newborns rotated their heads and trunk toward the appropriate loud speaker when hearing French but not English. These preliminary findings suggest that newborn crawling is not a simple stereotyped reflex under spinal control, but a complex pattern that can be modulated in response to higher-order, supra-spinally processed stimuli. The findings open fascinating questions about the range of stimuli to which newborn crawling is responsive.

Does rhythmic priming improve grammatical processing in Hungarian-speaking children with and without developmental language disorder?

Research has described several features shared between musical rhythm and speech or language, and experimental studies consistently show associations between performance on tasks in the two domains as well as impaired rhythm processing in children with language disorders. Motivated by these results, in the current study our first aim was to explore whether a short exposure to a regular musical rhythm (i.e., rhythmic priming) can improve subsequent grammatical processing in preschool-aged Hungarian-speaking children with and without developmental language disorder (DLD). Second, we investigated whether rhythmic priming is specific to grammar processing by assessing priming in two additional domains: a linguistic but non-grammatical task (picture naming) and a non-linguistic task (nonverbal Stroop task). Third, to confirm that the rhythmic priming effect originates from the facilitating effect of the regular rhythm and not the negative effect of the control condition, we added a third condition, silence, for all the three tasks. Both groups of children showed better performance on the grammaticality judgment task in the regular compared to both the irregular and the silent conditions but no such effect appeared in the non-grammatical and non-linguistic tasks. These results suggest that (1) rhythmic priming can improve grammatical processing in Hungarian, a language with complex morphosyntax, both in children with and without DLD, (2) the effect is specific to grammar and (3) is a result of the facilitating effect of the regular rhythm. These results could motivate further research about integrating rhythmic priming into traditional speech-language therapy. A video abstract of this article can be viewed at https://youtu.be/zKzGuIjZyvU.

Language familiarity influences own-race face recognition in 9- and 12-month-old infants.

During their first year, infants attune to the faces and language(s) that are frequent in their environment. The present study investigates the impact of language familiarity on how French-learning 9- and 12-month-olds recognize own-race faces. In Experiment 1, infants were familiarized with the talking face of a Caucasian bilingual German-French speaker reciting a nursery rhyme in French (native condition) or in German (non-native condition). In the test phase, infants' face recognition was tested by presenting a picture of the speaker's face they were familiarized with, side by side with a novel face. At 9 and 12 months, neither infants in the native condition nor the ones in the non-native condition clearly recognized the speaker's face. In Experiment 2, we familiarized infants with the still picture of the speaker's face, along with the auditory speech stream. This time, both 9- and 12-month-olds recognized the face of the speaker they had been familiarized with, but only if she spoke in their native language. This study shows that at least from 9 months of age, language modulates the way faces are recognized.

Fourteen-month-old infants track the language comprehension of communicative partners.

Infants employ sophisticated mechanisms to acquire their first language, including some that rely on taking the perspective of adults as speakers or listeners. When do infants first show awareness of what other people understand? We tested 14-month-old infants in two experiments measuring event-related potentials. In Experiment 1, we established that infants produce the N400 effect, a brain signature of semantic violations, in a live object naming paradigm in the presence of an adult observer. In Experiment 2, we induced false beliefs about the labeled objects in the adult observer to test whether infants keep track of the other person's comprehension. The results revealed that infants reacted to the semantic incongruity heard by the other as if they encountered it themselves: they exhibited an N400-like response, even though labels were congruous from their perspective. This finding demonstrates that infants track the linguistic understanding of social partners.

Infants' sensitivity to nonadjacent vowel dependencies: The case of vowel harmony in Hungarian.

Vowel harmony is a linguistic phenomenon whereby vowels within a word share one or several of their phonological features, constituting a nonadjacent, and thus challenging, dependency to learn. It can be found in a large number of agglutinating languages, such as Hungarian and Turkish, and it may apply both at the lexical level (i.e., within word stems) and at the morphological level (i.e., between stems and their affixes). Thus, it might affect both lexical and morphological development in infants whose native language has vowel harmony. The current study asked at what age infants learning an irregular harmonic language, Hungarian, become sensitive to vowel harmony within word stems. In a head-turn preference study, 13-month-old, but not 10-month-old, Hungarian-learning infants preferred listening to nonharmonic VCV (vowel-consonant-vowel) pseudowords over vowel-harmonic ones. A control experiment with 13-month-olds exposed to French, a nonharmonic language, showed no listening preference for either of the sequences, suggesting that this finding cannot be explained by a universal preference for nonharmonic sequences but rather reflects language-specific knowledge emerging between 10 and 13 months of age. We discuss the implications of this finding for morphological and lexical learning.

The specificity of the neural response to speech at birth.

In this work we ask whether at birth, the human brain responds uniquely to speech, or if similar activation also occurs to a non-speech surrogate 'language'. We compare neural activation in newborn infants to the language heard in utero (English), to an unfamiliar language (Spanish), and to a whistled surrogate language (Silbo Gomero) that, while used by humans to communicate, is not speech. Anterior temporal areas of the neonate cortex are activated in response to both familiar and unfamiliar spoken language, but these classic language areas are not activated to the whistled surrogate form. These results suggest that at the time human infants emerge from the womb, the neural preparation for language is specialized to speech.

I: INTRODUCTION.

The majority of the world's children grow up learning two or more languages. The study of early bilingualism is central to current psycholinguistics, offering insights into issues such as transfer and interference in development. From an applied perspective, it poses a universal challenge to language assessment practices throughout childhood, as typically developing bilingual children usually underperform relative to monolingual norms when assessed in one language only. We measured vocabulary with Communicative Development Inventories for 372 24-month-old toddlers learning British English and one Additional Language out of a diverse set of 13 (Bengali, Cantonese, Dutch, French, German, Greek, Hindi-Urdu, Italian, Mandarin, Polish, Portuguese, Spanish, and Welsh). We furthered theoretical understanding of bilingual development by showing, for the first time, that linguistic distance between the child's two languages predicts vocabulary outcome, with phonological overlap related to expressive vocabulary, and word order typology and morphological complexity related to receptive vocabulary, in the Additional Language. Our study also has crucial clinical implications: we have developed the first bilingual norms for expressive and receptive vocabulary for 24-month-olds learning British English and an Additional Language. These norms were derived from factors identified as uniquely predicting CDI vocabulary measures: the relative amount of English versus the Additional Language in child-directed input and parental overheard speech, and infant gender. The resulting UKBTAT tool was able to accurately predict the English vocabulary of an additional group of 58 bilinguals learning an Additional Language outside our target range. This offers a pragmatic method for the assessment of children in the majority language when no tool exists in the Additional Language. Our findings also suggest that the effect of linguistic distance might extend beyond bilinguals' acquisition of early vocabulary to encompass broader cognitive processes, and could constitute a key factor in the study of the debated bilingual advantage.

Acquisition of prosodic focus marking by English, French, and German three-, four-, five- and six-year-olds.

Previous research on young children's knowledge of prosodic focus marking has revealed an apparent paradox, with comprehension appearing to lag behind production. Comprehension of prosodic focus is difficult to study experimentally due to its subtle and ambiguous contribution to pragmatic meaning. We designed a novel comprehension task, which revealed that three- to six-year-old children show adult-like comprehension of the prosodic marking of subject and object focus. Our findings thus support the view that production does not precede comprehension in the acquisition of focus. We tested participants speaking English, German, and French. All three languages allow prosodic subject and object focus marking, but use additional syntactic marking to varying degrees (English: dispreferred; German: possible; French preferred). French participants produced fewer subject marked responses than English participants. We found no other cross-linguistic differences. Participants interpreted prosodic focus marking similarly and in an adult-like fashion in all three languages.

[Analysis of hepatitis C virus type and subtype distribution in Hungary]. / Magyarországi C-vírus-hepatitises betegek vírustípus- és szubtípusmegoszlásának elemzése.

INTRODUCTION: Hepatitis C virus (HCV) shows great structural variability. Based on genome sequencing and phylogenetical analysis, 7 types and 67 subtypes can be differentiated with varying geographical distribution. It is very important to determine the HCV type/subtype prior to starting direct antiviral therapy (DAA), which has been available since 2014, because the type, dose and optimal length of medication depends on these. AIM: In Hungary, the treatment of chronic HCV patients started in 1992 with the relevant special diagnostic tests being carried out in our Molecular Diagnostic Laboratory. Determination of the nucleotide sequence of the Hungarian HCV1b NS5A/PKR-BR region and the type and subtype distribution of Hungarian patients have already been carried out. The current summary discusses the results of 6092 chronic HCV patients (175 serotypes, 5917 genotypes) based on age, gender, regions and genotype distribution changes over the period between 1996 and 2017. METHOD: Serotyping (1996-1999). Genotyping: hybridization (2000-2016), real-time PCR (2016-; Cobas 4800 HCV GT). RESULTS: Genotype distribution: GT1a: 5.6%; GT1b: 84.6%; GT1a + 1b: 5.1%; GT2: 0.1%; GT3: 1.8%; GT4: 0.1%; mixed: 1.6%; GT1 (non-differentiated subtype): 1,1%. Women/men ratio: 52%/48%. The most common age category is 50-60 years (37% of all cases). There was no genotype asymmetry among the four Hungarian regions and Budapest. Over time, the prevalence of genotype 3 increased from 1.6% to 2.8% and the number of patients under the age of 40 doubled. CONCLUSION: There have been no substantial changes in the HCV type/subtype distribution in Hungary over the past 20 years, 1b remaining the most common. The introduction of real-time PCR method for genotyping has resulted in a major quality improvement including only a few mixed subtype results leading to more efficient drug selection. Orv Hetil. 2018; 159(Suppl 2): 2-8.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

The treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. The indication of therapy in patients with no contraindication is based on the demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Interferon-based or interferon-free therapies are available for the treatment. Due to their limited success rate as well as to their (sometimes severe) side-effects, the mandatory use of interferon-based therapies as first line treatment can not be accepted from the professional point of view. However, they can be used as optional therapy in treatment-naïve patients with mild disease. As of interferon-free therapies, priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund of Hungary and patients' organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv Hetil. 2018; 159(Suppl 1): 3-23.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5-0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24-37.

ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV.

BACKGROUND: The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. RESULTS: The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 and NCT01833533.).

Learning multiple rules simultaneously: Affixes are more salient than reduplications.

Language learners encounter numerous opportunities to learn regularities, but need to decide which of these regularities to learn, because some are not productive in their native language. Here, we present an account of rule learning based on perceptual and memory primitives (Endress, Dehaene-Lambertz, & Mehler, Cognition, 105(3), 577-614, 2007; Endress, Nespor, & Mehler, Trends in Cognitive Sciences, 13(8), 348-353, 2009), suggesting that learners preferentially learn regularities that are more salient to them, and that the pattern of salience reflects the frequency of language features across languages. We contrast this view with previous artificial grammar learning research, which suggests that infants "choose" the regularities they learn based on rational, Bayesian criteria (Frank & Tenenbaum, Cognition, 120(3), 360-371, 2013; Gerken, Cognition, 98(3)B67-B74, 2006, Cognition, 115(2), 362-366, 2010). In our experiments, adult participants listened to syllable strings starting with a syllable reduplication and always ending with the same "affix" syllable, or to syllable strings starting with this "affix" syllable and ending with the "reduplication". Both affixation and reduplication are frequently used for morphological marking across languages. We find three crucial results. First, participants learned both regularities simultaneously. Second, affixation regularities seemed easier to learn than reduplication regularities. Third, regularities in sequence offsets were easier to learn than regularities at sequence onsets. We show that these results are inconsistent with previous Bayesian rule learning models, but mesh well with the perceptual or memory primitives view. Further, we show that the pattern of salience revealed in our experiments reflects the distribution of regularities across languages. Ease of acquisition might thus be one determinant of the frequency of regularities across languages.

A cross-linguistic study of speech modulation spectra.

Languages show systematic variation in their sound patterns and grammars. Accordingly, they have been classified into typological categories such as stress-timed vs syllable-timed, or Head-Complement (HC) vs Complement-Head (CH). To date, it has remained incompletely understood how these linguistic properties are reflected in the acoustic characteristics of speech in different languages. In the present study, the amplitude-modulation (AM) and frequency-modulation (FM) spectra of 1797 utterances in ten languages were analyzed. Overall, the spectra were found to be similar in shape across languages. However, significant effects of linguistic factors were observed on the AM spectra. These differences were magnified with a perceptually plausible representation based on the modulation index (a measure of the signal-to-noise ratio at the output of a logarithmic modulation filterbank): the maximum value distinguished between HC and CH languages, with the exception of Turkish, while the exact frequency of this maximum differed between stress-timed and syllable-timed languages. An additional study conducted on a semi-spontaneous speech corpus showed that these differences persist for a larger number of speakers but disappear for less constrained semi-spontaneous speech. These findings reveal that broad linguistic categories are reflected in the temporal modulation features of different languages, although this may depend on speaking style.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient's organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3-22.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23-35.

The neural correlates of processing scale-invariant environmental sounds at birth.

Sensory systems are thought to have evolved to efficiently represent the full range of sensory stimuli encountered in the natural world. The statistics of natural environmental sounds are characterized by scale-invariance: the property of exhibiting similar patterns at different levels of observation. The statistical structure of scale-invariant sounds remains constant at different spectro-temporal scales. Scale-invariance plays a fundamental role in how efficiently animals and human adults perceive acoustic signals. However, the developmental origins and brain correlates of the neural encoding of scale-invariant environmental sounds remain unexplored. Here, we investigate whether the human brain extracts the statistical property of scale-invariance. Synthetic sounds generated by a mathematical model to respect scale-invariance or violate it were presented to newborns. In alternating blocks, the two sound types were presented together in an alternating fashion, whereas in non-alternating blocks, only one type of sound was presented. Newborns' brain responses were measured using near-infrared spectroscopy. We found that scale-invariant and variable-scale sounds were discriminated by the newborn brain, as suggested by differential activation in the left frontal and temporal areas to alternating vs. non-alternating blocks. These results indicate that newborns already detect and encode scale-invariance as a characteristic feature of acoustic stimuli. This suggests that the mathematical principle of efficient coding of information guides the auditory neural code from the beginning of human development, a finding that may help explain how evolution has prepared the brain for perceiving the natural world.

[Efficacy and safety of boceprevir based triple therapy in Hungarian patients with hepatitis C genotype 1 infection, advanced stage fibrosis and prior treatment failure]. / Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése elorehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertozött, korábban sikertelenül kezelt magyar betegeknél.

INTRODUCTION: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. AIM AND METHOD: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. RESULTS: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn's disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. CONCLUSIONS: With boceprevir based triple therapy, one of the bests available in 2011-2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366-1374.