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

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

Changing circumpolar distributions and isoscapes of Antarctic krill: Indo‐Pacific habitat refuges counter long‐term degradation of the Atlantic sector

The Southern Ocean provides strong contrasts in rates and directions of change in temperature and sea ice between its sectors, but it is unknown how these affect plankton species that are distributed right around Antarctica. Here, we quantify the changing circumpolar distributions of Antarctic krill, based on the CHINARE 2013/14 circum-Antarctic expedition, plus independent analyses of compiled abundance data (KRILLBASE:1926–2016). In the 1920s–1930s, average krill densities in the Atlantic-Bellingshausen sector were eight times those in the other sectors. More recently, however, the concentration factor has dropped to only about twofold. This reflects a rebalancing broadly commensurate with climatic forcing: krill densities declined in the Atlantic Bellingshausen sector which has warmed and lost sea ice, densities may have increased in the Ross-Pacific sector which showed the opposite climatic trend, while densities showed no significant changes in the more stable Lazarev-Indian sectors. Such changes would impact circumpolar food webs, so to better define these we examined circumpolar trends of isotopic values in krill and other zooplankton based on the CHINARE cruise and a literature meta-analysis. Krill δ15N values ranged significantly between sectors from 2.21‰ (Indian) to 3.59‰ (Ross-Pacific), about half a trophic level lower than another key euphausiid, Thysanoessa macrura. These isoscapes form a baseline for interpreting the reliance of predators on euphausiids, within the varying food webs around the continent. Overall, we suggest that the Indo-Pacific sector has acted as a refuge for the circumpolar krill stock while conditions for them deteriorated rapidly in the Atlantic sector

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

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

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

Acquired and congenital disorders of sung performance: A review.

Many believe that the majority of people are unable to carry a tune. Yet, this widespread idea underestimates the singing abilities of the layman. Most occasional singers can sing in tune and in time, provided that they perform at a slow tempo. Here we characterize proficient singing in the general population and identify its neuronal underpinnings by reviewing behavioral and neuroimaging studies. In addition, poor singing resulting from a brain injury or neurogenetic disorder (i.e., tone deafness or congenital amusia) is examined. Different lines of evidence converge in indicating that poor singing is not a monolithic deficit. A variety of poor-singing "phenotypes" are described, with or without concurrent perceptual deficits. In addition, particular attention is paid to the dissociations between specific abilities in poor singers (e.g., production of absolute vs. relative pitch, pitch vs. time accuracy). Such diversity of impairments in poor singers can be traced to different faulty mechanisms within the vocal sensorimotor loop, such as pitch perception and sensorimotor integration

Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis

[Background & Aims] Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis.[Methods] In this phase II, single-arm study, 59 patients with genotype 1–6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events.[Results] Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86–99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir.[Conclusions] Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis.[Lay summary] Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease.Clinical Trial Number: NCT03036852.Peer reviewe

Impact of direct‐acting antiviral agents on liver function in patients with chronic hepatitis C virus infection

© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan=99%, UK=78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course