fMRI Evidence for a Cortical Hierarchy of Pitch Pattern Processing

Pitch patterns, such as melodies, consist of two levels of structure: a global level, comprising the pattern of ups and downs, or contour; and a local level, comprising the precise intervals that make up this contour. An influential neuropsychological model suggests that these two levels of processing are hierarchically linked, with processing of the global structure occurring within the right hemisphere in advance of local processing within the left. However, the predictions of this model and its anatomical basis have not been tested in neurologically normal individuals. The present study used fMRI and required participants to listen to consecutive pitch sequences while performing a same/different one-back task. Sequences, when different, either preserved (local) or violated (global) the contour of the sequence preceding them. When the activations for the local and global conditions were contrasted directly, additional activation was seen for local processing in right planum temporale and posterior superior temporal sulcus (pSTS). The presence of additional activation for local over global processing supports the hierarchical view that the global structure of a pitch sequence acts as a “framework” on which the local detail is subsequently hung. However, the lateralisation of activation seen in the present study, with global processing occurring in left pSTS and local processing occurring bilaterally, differed from that predicted by the neuroanatomical model. A re-examination of the individual lesion data on which the neuroanatomical model is based revealed that the lesion data equally well support the laterality scheme suggested by our data. While the present study supports the hierarchical view of local and global processing, there is an evident need for further research, both in patients and neurologically normal individuals, before an understanding of the functional lateralisation of local and global processing can be considered established

An identification and brief advice programme for low-risk alcohol consumption in an acute medical setting: an implementation study.

OBJECTIVES: To implement an identification and brief advice (IBA) intervention to detect low-risk/hazardous alcohol consumption. DESIGN: Implementation was guided through the use of quality improvement tools and training. SETTING: This study was conducted over an 18-month period from April 2010 to September 2011 on a 42-bed acute medical unit at a central London acute hospital. PARTICIPANTS: All medical patients over the age of 18 admitted to the acute assessment unit were eligible; any patient unable to provide a medical history either through language barriers or due to illness was excluded. MAIN OUTCOME MEASURES: Percentage of medical patients admitted each week to the acute assessment unit who were screened for low-risk/hazardous alcohol consumption. RESULTS: Weekly data were analysed in time series run charts and cross-referenced to the date of educational sessions and their effect on the uptake of screening monitored. A demonstrable change in the mean percentage number of patients screened was observed in different time periods, 67.3-80.1%, following targeted teaching on the AAU. CONCLUSIONS: Our study demonstrates the successful use of quality improvement methodology to guide the implementation of Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), an IBA intervention, in the acute medical setting. The incorporation of the AUDIT-C into an admission document has been well accepted by the junior doctors, attaining an average (mean) of 80% of patients being screened using the tool. Targeted teaching of clinical staff involved in admitting patients appears to be the most effective method in improving uptake of IBA by junior doctors

Mooring systems for marine energy converters

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this record.This paper discusses several new technologies for mooring floating marine energy converter (MEC) devices, such as wave energy generators, tidal current turbines and floating wind turbines. The principal mooring component is a special nylon fiber rope which provides cyclic tension fatigue endurance much superior to that of conventional nylon ropes. The nylon fiber is treated with a new proprietary coating which has excellent wet yarn abrasion properties. The parallel-subrope type rope construction further reduces internal abrasion. Extensive laboratory testing was carried out on this new nylon rope design. Cyclic tension fatigue tests were conducted at mean loads and load amplitudes typical of actual service conditions and at higher mean loads and amplitudes. These tests demonstrate that the special nylon rope has essentially the same, desirable stretch characteristics as conventional nylon rope and has much better endurance performance. The mooring connection to the floating MEC device consists of a high-modulus fiber rope pendant which passes through a low-friction bell-mouth nylon fairlead on the MEC device. This eliminates the use of heavy, unreliable chain in this critical connection. A unique bag anchor system would be used on sand, clay, rock and other sea beds in which conventional drag embedment anchors and driven piles are impractical. The bag anchor consists of a large abrasion resistant carcass with lifting straps and top closure. The bag is transported to site in a collapsed form and is filled with local sand or aggregate to provide ballast weight. Several or many such bags are enclosed within a fiber rope net for deployment and are grouped together for connection to the mooring line. The paper will be of particular interest to designers of moorings for MEC systems in shallow water and severe wave environments. It will also be of interest for other mooring applications.This work would not have been possible without the funding and support of the Scottish Government, the Carbon Trust and Innovate UK.   The project was funded under the Marine Renewables Commercialization Fund (MRCF) and Marine Energy Supporting Array Technologies (MESAT).   Other partners who contributed to this project include Lloyd’s Register, DNV‐GL, TenCate, Orion Energy Centre, Nylacast, and offshore wind developer IDEOL.    Input and encouragement was provided by tidal power developer partner Bluewater, and wave energy developers AWS Ocean Energy and Pelamis.

Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase

Objective In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. Design Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-γ (IFN-γ) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. Results MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-γ stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. Conclusions Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death

Sensitivity to musical emotion is influenced by tonal structure in congenital amusia

Emotional communication in music depends on multiple attributes including psychoacoustic features and tonal system information, the latter of which is unique to music. The present study investigated whether congenital amusia, a lifelong disorder of musical processing, impacts sensitivity to musical emotion elicited by timbre and tonal system information. Twenty-six amusics and 26 matched controls made tension judgments on Western (familiar) and Indian (unfamiliar) melodies played on piano and sitar. Like controls, amusics used timbre cues to judge musical tension in Western and Indian melodies. While controls assigned significantly lower tension ratings to Western melodies compared to Indian melodies, thus showing a tonal familiarity effect on tension ratings, amusics provided comparable tension ratings for Western and Indian melodies on both timbres. Furthermore, amusics rated Western melodies as more tense compared to controls, as they relied less on tonality cues than controls in rating tension for Western melodies. The implications of these findings in terms of emotional responses to music are discussed

Abnormal neural responses to harmonic syntactic structures in congenital amusia

Harmonic syntactic structures are organized hierarchically through local and long-distance dependencies. The present study investigated whether the processing of harmonic syntactic structures is impaired in congenital amusia, a neurodevelopmental disorder of pitch perception. Harmonic sequences containing two phrases were used as stimuli, in which the first phrase ended with a half cadence and the second with an authentic cadence. In Experiment 1, we manipulated the ending chord in the authentic cadence to be either syntactically regular or irregular. Sixteen amusics and 16 controls judged the expectedness of these chords while their EEG waveforms were recorded. In comparison to the regular endings, irregular endings elicited an ERAN, an N5 and a late positive component in controls but not in amusics, indicating that amusics were impaired in perceiving harmonic syntactic structures induced by local dependencies. In Experiment 2, we manipulated the half cadence of the harmonic sequences to examine the processing of harmonic syntactic structures induced by long-distance dependencies. An ERAN-like response and an N5 were elicited in controls but not in amusics, suggesting that amusics were impaired in processing long-distance syntactic dependencies. Furthermore, for controls, the neural processing of local and long-distance syntactic dependencies was correlated in the late (as indexed by the N5) but not in the early stage. These findings indicate that amusics are impaired in the detection of syntactic violations and subsequent harmonic integration. The implications of these findings in terms of hierarchical music-syntactic processing are discussed

Practicing a Musical Instrument in Childhood is Associated with Enhanced Verbal Ability and Nonverbal Reasoning

Background: In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related. Methodology/Principal Findings: Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities. Conclusions/Significance: While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverba

Proteomic Analysis of the Dysferlin Protein Complex Unveils Its Importance for Sarcolemmal Maintenance and Integrity

Dysferlin is critical for repair of muscle membranes after damage. Mutations in dysferlin lead to a progressive muscular dystrophy. Recent studies suggest additional roles for dysferlin. We set out to study dysferlin's protein-protein interactions to obtain comprehensive knowledge of dysferlin functionalities in a myogenic context. We developed a robust and reproducible method to isolate dysferlin protein complexes from cells and tissue. We analyzed the composition of these complexes in cultured myoblasts, myotubes and skeletal muscle tissue by mass spectrometry and subsequently inferred potential protein functions through bioinformatics analyses. Our data confirm previously reported interactions and support a function for dysferlin as a vesicle trafficking protein. In addition novel potential functionalities were uncovered, including phagocytosis and focal adhesion. Our data reveal that the dysferlin protein complex has a dynamic composition as a function of myogenic differentiation. We provide additional experimental evidence and show dysferlin localization to, and interaction with the focal adhesion protein vinculin at the sarcolemma. Finally, our studies reveal evidence for cross-talk between dysferlin and its protein family member myoferlin. Together our analyses show that dysferlin is not only a membrane repair protein but also important for muscle membrane maintenance and integrity