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Aim\ud\udLung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.\udMethod\ud\udMultidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis.\udResults\ud\udFrom 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.\udConclusion\ud\udPatients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Background Crohn’s disease (CD), an idiopathic inflammatory bowel disease (IBD), has been recently shown to increase the risk of developing type 2 diabetes (T2D). Moreover, treatment with anti-diabetic drugs has a protective role in preventing the severity and course of CD progression. However, the pathophysiological basis of T2D development in CD remains unclear. Findings have highlighted the contribution of adipose tissue (AT) to the development of chronic inflammatory diseases and have identified parallels between T2D and CD that may provide hints to common mechanisms of disease pathogenesis. Typically, microbial dysbiosis, hyperpermeable intestinal barrier, and intra-abdominal AT accumulation are the common features of both diseases, yet how the interplay of these factors contribute to pathogenesis is not known. Therefore, common pathogenic paradigms underlying both T2D and CD have led us to hypothesize that chronic intestinal inflammation serves as an initiator of AT dysfunction in CD, predisposing individuals to T2D. Further, the lack of appropriate animal models of CD with chronic intestinal inflammation that manifests accumulation of intra-abdominal AT, and extra-intestinal metabolic disorder as observed in CD and T2D patients has been a limitation. Purpose To develop a genetic mouse model to investigate if gut inflammation-mediated microbial dysbiosis and metabolic dysregulation of AT are at the nexus that cause T2D in CD. Method We developed a CD-mouse model, where we challenged Nod2-deficient mice (NOD2 being the strongest genetic risk factor contributing to CD) with a chronic inflammatory insult regime, using dextran sulfate sodium (cDSS) for 3 cycles. Subsequently, intraperitoneal insulin and oral glucose tolerance tests, metabolic caging, and MRI imaging of mice were performed. Changes in AT metabolism and microbial infiltration into AT were analyzed by quantitative real-time PCR (qRT-PCR) and/or immunohistochemistry (IHC). Result(s) Our new CD-mouse model revealed increased gut inflammation (TNF and type-I IFN) in Nod2-deficient mice compared to wild-type control mice post-cDSS. Surprisingly, Nod2-deficient mice gained body weight, which was at least in part accounted for by an increased intra-abdominal AT accumulation along with decreased AT fatty-acid metabolism (Cpt1a, Fabp4 expression) and AT browning (Ucp1, Cidea expression, and UCP-1 staining), reduced intestinal goblet cell numbers, increased gut bacterial infiltration within the fat, more insulin resistance and energy expenditure. Conclusion(s) This experimental mouse model mimicking CD-associated T2D will provide insights into how the microbiome-AT axis fuel chronic inflammation-mediated extra-intestinal metabolic disorder and immune dysregulation. Understanding these connections will be transformative, as it will help us devise novel therapeutic strategies to prevent T2D development in progressive CD patients. Disclosure of Interest None Declared

Contains fulltext : 283152.pdf (Publisher’s version ) (Open Access) INTRODUCTION: The Newborn Life Support (NLS) guideline aims to provide healthcare professionals a consistent approach during neonatal resuscitation. Adherence to this and analogous guidelines has repetitively been proven to be difficult.This study evaluates adherence to guideline using a novel augmented reality (Microsoft HoloLens) electronic decision support tool during standardized simulated neonatal resuscitation compared with subjects working from memory alone. METHODS: In this randomized controlled pilot study, 18 professionals responsible for neonatal resuscitation were randomized to the intervention group and 11 to the control group. Demographic characteristics were similar between both groups. A standardized neonatal resuscitation scenario was performed, which was recorded and later assessed for adherence to the NLS algorithm by 2 independent reviewers. Secondary outcomes were error classification in case of algorithm deviation and time to the execution or completion of critical steps in the algorithm to determine delay. RESULTS: Median (interquartile range) scores of a theoretical maximum of 40 in the intervention group were 34 (32.5-35.5) versus 29 (27-33) in the control group ( P = 0.004). Errors of commission were committed less frequently with the electronic decision support tool 2 (1-2.5) compared with 4 (2-4) in the control group ( P = 0.029). Analysis of time to initiation or completion of key steps in the NLS algorithm showed no significant differences between both groups. CONCLUSIONS: Healthcare professionals using an electronic decision support tool showed improved adherence to the NLS guideline during simulated neonatal resuscitation.

The suspension of use of sub-urethral mesh in the UK in 2018 has seen the resurgence of colposuspension in female SUI surgery. Open and laparoscopic colposuspension techniques are well recognised. We present data from 28 robotic-assisted laparoscopic colposuspension (RALCp) procedures, reporting on technique, safety and efficacy. Approval was obtained from the hospital New and Novel Procedures Committee. All patients had urodynamic assessment prior to surgery. Data was prospectively gathered and 24-h pad usage and Urinary Incontinence Short Form Questionnaire (ICIQ-UI-SF) scores were used to assess symptom severity and quality of life. PGII scores were used to assess patient satisfaction after the procedure. Paired T test analysis was conducted. Since May 2019, robotic colposuspension has been performed in 28 patients. The mean age and BMI were 49 and 27 (kg/m

Background: Pediatric posterior fossa ependymoma contributes to morbidity and mortality in children. Following gross total resection and adjuvant radiotherapy, there is a known risk of local recurrence that portends a dismal prognosis. We sought to characterize survival in a molecularly defined cohort with an emphasis on recurrence patterns that influence outcome. Methods: This study was approved by the Ethics Board of the Hospital for Sick Children. We performed a twenty-year single-center retrospective study to identify clinical, demographic and treatment characteristics of patients with pathologically diagnosed posterior fossa ependymoma. Results: There were 60 patients identified that underwent primary resection. Recurrence rate in the cohort was 48% with 29 cases of recurrent ependymoma occurring at a mean time of 24 months after index surgery. No mortalities were observed among patients undergoing primary resection without recurrent disease. Median cohort survival was 12.3 years in the primary cohort and and 6.32 years among patients recurrent ependymoma. Recurrent disease was significantly associated with worse overall survival after multivariate analysis (HR = 0.024). Conclusions: We highlight overall survival and factors influencing mortality in pediatric posterior fossa ependymoma. Recurrent disease confers a worse prognosis. We describe for the first time survival trends following local and distant recurrences managed through multiple resections.

The past two decades have witnessed a resurgence in neutrophil research, inspired in part by the discovery of neutrophil extracellular traps (NETs) and their myriad roles in health and disease. Within the lung, dysregulation of neutrophils and NETosis have been linked to an array of diseases including pneumonia, cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and severe asthma. However, our understanding of pathologic neutrophil responses in the lung remains incomplete. Two methodologic issues have contributed to this gap: first, an emphasis on studying neutrophils from blood rather than the lung and second, the technical difficulties of interrogating neutrophil responses in mice, which has largely restricted basic murine research to specialized laboratories. To address these limitations, we have developed a suite of techniques for studying neutrophil effector functions specifically in the mouse lung. These include ex vivo assays for phagocytosis and NETosis using bronchoalveolar neutrophils and in situ evaluation of NETosis in a murine model of pneumonia. Throughout, we have prioritized technical ease and robust, quantitative readouts. We hope these assays will help to standardize research on lung neutrophils and improve accessibility to this burgeoning field.

BACKGROUND: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.METHODS: This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m 2 twice daily on days 1–14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.FINDINGS: Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37–60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6–59·1) in the capecitabine group compared with 36·4 months (29·7–44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63–1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55–0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30–44) in the observation group (adjusted HR 0·75, 95% CI 0·58–0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6–35·9) in the capecitabine group and 17·5 months (12·0–23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8–46·3) in the capecitabine group and 17·4 months (12·0–23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (INTERPRETATION: Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.FUNDING: Cancer Research UK and Roche.

Discriminating temporal relationships in speech is crucial for speech and language development. However, temporal variation of vowels is difficult to perceive for young infants when it is determined by surrounding speech sounds. Using a familiarization-discrimination paradigm, we show that English-learning 6- to 9-month-olds are capable of discriminating non-native acoustic vowel duration differences that systematically vary with subsequent consonantal durations. Furthermore, temporal regularity of stimulus presentation potentially makes the task easier for infants. These findings show that young infants can process fine-grained temporal aspects of speech sounds, a capacity that lays the foundation for building a phonological system of their ambient language(s).

Despite their acoustic similarities, human infants are able to discriminate between infant-directed song (as produced by human adults) and infant-directed speech in both English and Russian. However, experimenters are somewhat limited in what they can test using the preference paradigm with infants. As a complement to a previous infant study (Tsang et al. 2016), we asked whether a songbird, the zebra finch, could discriminate infant directed song and speech in English and Russian, and tested responses to stimuli that humans could not categorize as either type. Male and female zebra finches learned to discriminate the stimuli in both languages equally well, although females were slightly faster at learning the discrimination, and generalized responses to untrained stimuli of the same categories. Bird responses to stimuli that humans could not categorize likewise did not follow a clear pattern. Our results show that infant-directed song and speech are discriminable as categories by non-humans, that song and speech are as easy to discriminate in English and Russian, and that comparative studies together can provide more complete answers to research questions about auditory perception and acoustic features used for discrimination than using one species or one language alone.

Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more effective than similar postoperative treatment for oesophageal, gastric, and rectal cancers, perhaps because of more effective micrometastasis eradication and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to investigate the feasibility, safety, and efficacy of preoperative chemotherapy for colon cancer. Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced (T3 with >= 5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m(2), l-folinic acid 175 mg, fluorouracil 400 mg/m(2) bolus, then 2400 mg/m(2) by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the first 6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of defunctioning colostomy as stratification variables. Primary outcome measures of the pilot phase were feasibility, safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat. This trial is registered, number ISRCTN 87163246. Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3-4 gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with no significant differences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99) versus 12% (six of 51) had complications prolonging hospital stay (p=0.81). 98% (50 of 51) of postoperative chemotherapy patients had T3 or more advanced tumours confirmed at post-resection pathology compared with 91% (90 of 99) of patients following preoperative chemotherapy (p=0.10). Preoperative therapy resulted in significant downstaging of TNM5 compared with the postoperative group (p=0.04), including two pathological complete responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p

several reports have noted significant associations among phonological awareness, early reading skills, and music perception skills in young children. We examined whether music processing skills differentially predicted reading performance in a broad age range of 69 children with and without formal music training. Pitch perception was correlated with phonological awareness, a finding consistent with the hypothesis that basic auditory processing skills underlie the association between music and reading abilities. Nevertheless, the correlation between music skills and reading skills was affected by the presence of formal music training: pitch discrimination predicted reading ability only in children without formal music training. Studies examining the association between music perception and reading (and perhaps other cognitive domains as well) should not ignore the factor of music training.

Singing is a ubiquitous human behavior and plays a significant role in human culture and socialization. Research on children's singing has focused on music instruction techniques for developing singers, yet little is known about the developmental mechanisms underlying singing acquisition. Recently, Berkawska and Dalla Bella (2009a) proposed a sensorimotor loop model of singing to explain poor singing ability in the adult population. Here, we review the literature on the development of singing during childhood in the context of the sensorimotor loop model of singing. KEYWORDS - singing, development, children, auditory perception, motor function Singing is widely regarded as a universal human behavior (Dowling, 1984; Welch, 1994) that serves a number of important social functions. Singing is an effective means of transmitting cultural knowledge and social customs (Chatwin, 1987; Cong-HuyenTon-Nu, 1979). Singing is also used to ease the pressures of everyday life. For example, many workers use song to accompany work activities, especially those requiring the synchronization of repetitive movements (Cong-Huyen-Ton-Nu, 1979; Keil, 1979). Singing is often an important part of courtship, and it has been proposed that robust musical calls may signal the possession of healthy, appealing genes to prospective mates (e.g., Huron, 2001). In general, singing can promote social cohesion, reinforce cherished values and ideals, foster shared identity, and promote "emotional contagion" (Booth, 1981; Peretz, 2006). Finally, singing plays a critical role in child rearing and the caregiver-infant bond. Lullabies and playsongs are found in all known cultures, suggesting that they serve an important function in maternal child care (Trehub, 2000; Trehub & Trainor, 1998). Despite the importance of singing in both human development and human culture, there has been relatively little empirical research on the acquisition of singing during childhood. Singing is thought to emerge spontaneously without formal instruction during early child development (Dalla Bella, Giguere, & Peretz, 2007) and many studies over the last 30 years have documented a relatively orderly progression of the acquisition of specific singing abilities during childhood (e.g., see Welch, 2006 for a review). However, the developmental mechanisms underlying singing acquisition during childhood are still not well understood. Although there is general agreement that both maturational and experiential factors affect singing development (e.g., Davidson, McKernon, & Gardner, 1981; Stadler-Elmer, 2006; Welch, 1985), there are few empirical studies of how these factors interact. Welch (1986) proposed a model of singing acquisition in which children's singing behaviors appear in a fixed order from Stage 1, where the words of a song are the initial center of interest rather than the melody, to Stage 5, where there are no significant melodic or pitch errors in a child's vocal productions. Presumably this progression is impacted by culture, practical experience, and genetically-driven maturation. Detailed study of singing development requires, first, a definition of singing and, second, a notion of what constitutes mature singing behavior. With respect to the first question, Welch (1994) noted that the judgment of an utterance to be speech or song "is defined by a complex web of interacting factors encompassing perception, cognition, physical development, maturation, society, culture, history and intentionality" (p. 3). Early in development, singing and talking may be less differentiated than later. Indeed, infant-directed speech is often referred to as musical speech because of its exaggerated pitch contours, rhythmic patterning and repetition (Fernald, 1991). The boundaries between speech and song can be even less clear in the vocalizations of infants and young children, and determination is muddied by the fact that adults often attempt to over interpret infant vocalizations (Welch, 1994). …

Preverbal infants are attuned to the different emotional messages contained in playsongs and lullabies. However, it is unclear which performance properties of singing underlie infants' perception of the communicative intent of infant-directed singing. Volkova, Trehub, and Schellenberg (2006) recently demonstrated that 6- and 7-month-old infants preferred low-pitched to high-pitched renditions of lullabies, suggesting that pitch may be one performance characteristic that conveys the communicative intent in infant-directed singing. In the current study, we evaluated 6- and 7-month-old infants' natural preferences for unfamiliar, expressive lullabies and playsongs as a function of pitch using a head-turn preference procedure. Infants preferred low-pitched over high-pitched versions of lullabies and high-pitched over low-pitched versions of playsongs. Results suggest that the overall pitch of a song is communicative to infants and that the affective nature of music can have an effect on infants' pitch preferences. That is, infants' preferences for pitch are context-dependent.

In their everyday communication, parents do not only speak but also sing with their infants. However, it remains unclear whether infants' can discriminate speech from song or prefer one over the other. The present study examined the ability of 6- to 10-month-old infants (N = 66) from English-speaking households in London, Ontario, Canada to discriminate between auditory stimuli of native Russian-speaking and native English-speaking mothers speaking or singing to their infants. Infants listened significantly longer to the sung stimuli compared to the spoken stimuli. This is the first study to demonstrate that, even in the absence of other multimodal cues, infant listeners are able to discriminate between sung and spoken stimuli, and furthermore, prefer to listen to sung stimuli over spoken stimuli.

The preferences of 2- and 4-month-old infants for consonant versus dissonant two-tone intervals was tested by using a looking-time preference procedure. Infants of both ages preferred to listen to consonant over dissonant intervals and found it difficult to recover interest after a sequence of dissonant trials. Thus, sensitivity to consonance and dissonance is found before knowledge of scale structure and may be based on the innate structure of the inner ear and the firing characteristics of the auditory nerve. It is likely that consonance perception provides a bootstrap into the task of learning the pitch structure of the musical system to which the infant is exposed.

The zinc-binding proteins (ZnBPs) in porcine brain were characterized by the radioactive zinc-blot technique. Three ZnBPs of molecular weights about 53 kDa, 42 kDa, and 21 kDa were identified. The 53 kDa and 42 kDa ZnBPs were found in all subcellular fractions while the 21 kDa ZnBP was mainly associated with particulate fractions. This 21 kDa ZnBP was identified by internal protein sequence data as the myelin basic protein. Further characterization of its electrophoretic properties and cyanogen bromide cleavage pattern with the authentic protein confirmed its identity. The zinc binding properties of myelin basic protein are metal specific, concentration dependent and pH dependent. The zinc binding property is conferred by the histidine residues since modification of these residues by diethyl-pyrocarbonate would abolish this activity. Furthermore, zinc ion was found to potentiate myelin basic protein-induced phospholipid vesicle aggregation. It is likely that zinc plays an important role in myelin compaction by interacting with myelin basic protein.

The temporal and spatial changes of intracellular free calcium ([Ca2+]i) within the cytosol and nucleis of C6 glioma cells have been investigated with laser confocal scanning microscopy to evaluate the current view that Ca2+ ions pass freely through nuclear pores by diffusion. Our results indicate that localized cytosolic Ca2+ release, which appeared as puffs, spread with an apparent diffusion rate of 0.35 +/- 0.07 microns/sec (n = 44). This release was followed by an immediate Ca2+ uptake at the resting stage. Following the treatment with thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase, release of nuclear Ca2+ from certain nuclear hot zones and nuclear envelope was obtained. Most of the nuclear Ca2+ released were confined to the nuclear boundary, but a slow migration of Ca2+ towards the cytosol was observed. The apparent diffusion rate of this Ca2+ release is 0.015 microns/sec. By contrast, the inward spread into nucleus occurred with a diffusion rate of 0.04 microns/sec. From these diffusion rates and other experimental evidence, we conclude that the movement of Ca2+ at the nucleocytosolic interface is more than a simple diffusion process and the interface is a barrier to Ca2+ movement.

Caregivers around the world sing to their infants. Infants not only prefer to listen to infant-directed singing over adult-directed singing, but infant-directed singing also serves a function, communicating affective information to preverbal infants to aid in adjusting arousal levels. Pitch variation has previously been identified as one performance feature that may help to convey the message. Earlier research has indicated that infants' pitch preferences are context dependent, suggesting that infants are tuned in to the communicative intent of infant-directed singing. However, there are several other performance-based features present in infant-directed singing that may also contribute to the affective message. The current study examined the role of context on infants' tempo preferences in sung playsongs and lullabies. Using a head-turn preference procedure, we measured 24 preverbal infants' natural preferences for foreign language playsongs and lullabies as a function of tempo. Infants showed a preference for fast over slow tempo playsongs, but no such context dependent preference was found within lullabies. Results partially support the role of tempo as a communicative feature of infant directed singing. Keywords: infant perception, music perception, tempo perception Music is often used to express and elicit emotions (Juslin & Sloboda, 2001). Basic emotions such as happiness and sadness are easily attributed to musical pieces by both adult listeners (Cupchik, Rickert, & Mendelson, 1982) and young children (Trainor & Trehub, 1992). Clearly music has the potential to convey emotional information to listeners of various ages. The use of music as a means of emotional expression may be especially important to infant listeners. Caregivers' singing to their infants is a universal phenomenon (Brakeley, 1950; Trehub & Schellenberg, 1995), and infants demonstrate a clear attraction to maternal singing compared with maternal speech (Nakata & Trehub, 2004). Furthermore, infants show a preference for infant-directed singing compared with infant-absent singing (Trainor, 1996), and this preference is present in newborns (Masataka, 1999). One proposed function of infant-directed singing is to communicate affective information to preverbal infants to adjust their arousal levels (Trainor, 1996; Trehub & Schellenberg, 1995; Trehub, Trainor, & Unyk, 1993). However, the performance-based features of infantdirected singing that convey the message are unclear. While numerous studies have indicated that pitch is an informative performance based aspect of singing (Trainor, 1996; Trehub et al., 1993; Tsang & Conrad, 2010), other performance-based characteristics of infant-directed singing, such as rhythm and tempo, may also be informative to the infant. The present study addressed this issue by examining whether infants' preferences for tempo are contextdependent. Infant-directed songs can generally be categorized into two major song types: playsongs and lullabies. Each song type has characteristic performance features. Playsongs are characterized by high rhythmicity, high pitch level, and fast tempo and are often employed by caregivers to arouse and stimulate their infant (Rock, Trainor, & Addison, 1999). In contrast, lullabies are often used to calm and soothe an infant to make them ready for sleep (Trehub & Trainor, 1998) and are typically sung at a lower pitch and slower tempo in comparison to playsongs. Trainor (1996) demonstrated that these performance features are perceptually discriminable to adult listeners, who were able to correctly categorize playsongs as playsongs and lullabies as lullabies. In addition, playsongs and lullabies elicit different behavioral responses from infants. Listening to playsongs often leads young infants to display outward behaviors and look to their caregivers more often, whereas listening to lullabies generally leads to infants directing their attention inward (Rock et al. …

N.D. James, M.R. Sydes, M.D. Mason, N.W. Clarke, D.P. Dearnaley, M.R. Spears, R. Millman, C.C. Parker, A.W.S. Ritchie, J.M. Russell, J. Staffurth, R.J. Jones, R. Cathomas, A. Robinson, S. Chowdhury, D. Tsang, S. Brock, O. Parikh, J.D. Graham, M.K.B. Parmar. Warwick University, Clinical Trials Unit, Coventry, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Institute for Clinical Trials and Methodology, London, United Kingdom; Cardiff University, School of Medicine, Cardiff, United Kingdom; The Christie NHS Foundation Trust, Department of Urology, Manchester, United Kingdom; The Institute of Cancer Research and Royal Marsden Hospital NHS Trust, Academic Unit of Radiotherapy, London, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Patient Representative, NA, United Kingdom; The Royal Marsden Hospital, Department of Radiotherapy, London, United Kingdom; Beatson West of Scotland Cancer Centre, Institute of Cancer Sciences, Glasgow, United Kingdom; Cardiff University and Velindre NHS Trust, School of Medicine, Cardiff, United Kingdom; Kantonsspital Graubunden, Department of Oncology, Chur, Switzerland; Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom; Guy’s Hospital, Department of Medical Oncology, London, United Kingdom; Southend & Basildon Hospitals, Department of Oncology, Southend, United Kingdom; Poole Hospital NHS Foundation Trust and Royal Bournemouth Hospital NHS Foundation Trust, Department of Oncology, Poole, United Kingdom; East Lancashire Hospitals NHS Trust, Department of Oncology, Blackburn, United Kingdom; Musgrove Park Hospital, Oncology and Haematology Clinical Trials Unit, Taunton, United Kingdom

We show that infants’ long-term memory representations for melodies are not just reduced to the structural features of relative pitches and durations, but contain surface or performance tempo- and timbre-specific information. Using a head turn preference procedure, we found that after a one week exposure to an old English folk song, infants preferred to listen to a novel folk song, indicating that they remembered the familiarized melody. However, if the tempo (25% faster or slower) or instrument timbre (harp vs. piano) of the familiarized melody was changed at test, infants showed no preference, indicating that they remembered the specific tempo and timbre of the melodies. The results are consistent with an exemplar-based model of memory in infancy rather than one in which structural features are extracted and performance features forgotten.