Ultra-high resolution X-ray structures of two forms of human recombinant insulin at 100 K

The crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (λ = 0.77 Å). Refinement carried out with anisotropic displacement parameters, removal of main-chain stereochemical restraints, inclusion of H atoms in calculated positions, and 220 water molecules, converged to a final value of R = 0.1112 and Rfree = 0.1466. The structure includes what is thought to be an ordered propanol molecule (POL) only in chain D(4) and a solvated acetate molecule (ACT) coordinated to the Zn atom only in chain B(2). Possible origins and consequences of the propanol and acetate molecules are discussed. Three types of amino acid representation in the electron density are examined in detail: (i) sharp with very clearly resolved features; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry; (iii) poor density and difficult or impossible to model. An example of type (ii) is observed for the intra-chain disulphide bridge in chain C(3) between Sγ6–Sγ11 which has two clear conformations with relative refined occupancies of 0.8 and 0.2, respectively. In contrast the corresponding S–S bridge in chain A(1) shows one clearly defined conformation. A molecular dynamics study has provided a rational explanation of this difference between chains A and C. More generally, differences in the electron density features between corresponding residues in chains A and C and chains B and D is a common observation in the Insugen (I) structure and these effects are discussed in detail. The crystal structure, also at 0.92 Å and 100 K, of a second commercially available form of human recombinant insulin, Intergen (II), deposited in the Protein Data Bank as 3W7Y which remains otherwise unpublished is compared here with the Insugen (I) structure. In the Intergen (II) structure there is no solvated propanol or acetate molecule. The electron density of Intergen (II), however, does also exhibit the three types of amino acid representations as in Insugen (I). These effects do not necessarily correspond between chains A and C or chains B and D in Intergen (II), or between corresponding residues in Insugen (I). The results of this comparison are reported

Identifying the Cognitive Mechanisms that Mediate the Analgesic Benefits of Music Listening Interventions using the Cognitive Vitality Model

Overall, this thesis presents a theoretical model of the cognitive mechanisms involved in analgesic MLIs, followed by three empirical studies. The scoping review presented in Chapter 2 introduces a comprehensive overview of five cognitive mechanisms and how they fit together to form the Cognitive Vitality Model. Initially, at a lower level, music captures our attention. Following this a person uses their Cognitive Agency to actively engage with the music listening experience. Processes of Enjoyment and Meaning Making, contribute to an intrinsically rewarding experience which motivates the person to continue listening until they become completely absorbed in the music. When patients become fully immersed they integrate the music with their pain, which makes it less unpleasant and less intense. Instead the person becomes more connected with aspects of their self that are reflected in the music, which leads to a strengthened sense of self, and ultimately a greater level of Cognitive Vitality. The development of the Cognitive Vitality Model helped to generate testable hypotheses in relation to the relative impact of each specific mechanism. Based on the findings from the scoping review presented in Chapter 2, empirical methods were to explore three specific mechanisms (Automated Attention, Cognitive Agency and Enjoyment and Meaning Making). The impact of Cognitive Agency was demonstrated in the audio feature analysis presented in Chapter 3 which identified that people choose music with different intramusical features compared to music chosen by experimenters. Subsequently, the limit of Automated Attention was highlighted in the behavioural experiment presented in Chapter 4 which highlighted that intramusical features alone cannot account for the analgesic effects of music listening. Importantly this was the first study to isolate the role of making a choice on the analgesic benefits of music listening, independently but alongside the benefits attributable to Enjoyment. Accordingly, top-down processes in music interventions should be continued to be explored in the context of music-based pain management strategies. Lastly the field study presented in Chapter 5 was used to examine the external validity of the Cognitive Vitality Model with a clinical population. Chronic pain patients were in agreement that musical absorption mediates the analgesic benefits of self-chosen music, and helps to elicit a strengthened sense of self. While one of the main strengths of this thesis is that it provides an overarching evidence-based model of the cognitive mechanisms involved in MLIs it is important to recognize some of the methodological limitations including the validity of using Spotify audio features from a psychological perspective. Areas for future research in this area were dutifully considered in light of current conceptualisations of enjoyment and the potential for additional behavioural experiments. Overall, these findings contribute greater insight into the cognitive mechanisms involved in mediating the analgesic benefits of self-chosen music

The Audio-Visual Aesthetics of Music and Dance

Dance and music appear to belong together: Conventional definitions of dance often con­ ceive it as a rhythmical activity in which a series of steps is performed to musical accom­ paniment. Indeed, dance and music share many similarities such as rhythm and may have co-evolved as a form of nonverbal communication between groups of people. Despite a rich history of composers and choreographers exploring the aesthetic relationship be­ tween dance and music, only a few scientific studies have systematically explored how the visual aesthetics of dance interact with the auditory aesthetics of sound and music. In this chapter we will focus on such interactions; we will explore the common evolutionary origins of dance and music and review existing research on how dance and music influ­ ence each other to produce an audio-visual aesthetics of sound and movement. The chap­ ter will explore interactions in both directions: music influences dance perception by al­ tering movement expressiveness, orienting visual attention, and by modulating memory. At the same time music perception strongly depends on groove and danceability and is shaped by the listener’s dance experience. The chapter closes with a review of method­ ological challenges to studying the audio-visual aesthetics of dance and music and sug­ gestions for future research in this field

Tune out pain: Agency and active engagement predict decreases in pain intensity after music listening

Music is increasingly being recognised as an adjuvant treatment for pain management. Music can help to decrease the experience of both chronic and experimental pain. Cognitive agency has been identified as a specific mechanism that may mediate the analgesic benefits of music engagement however, it is unclear if this specific mechanism translates to acute pain. Previous attempts to understand the cognitive mechanisms that underpin music analgesia have been predominantly lab-based, limiting the extent to which observed effects may apply to participants\u27 everyday lives. Addressing these gaps, in naturalistic settings, the present study examined the degree to which cognitive agency (i.e., perceived choice in music), music features (i.e., complexity), and individual levels of musical sophistication were related to perceived pain. In an online global experiment, using a randomised between groups experimental design with two levels for choice (no choice and perceived choice) and two levels for music (high and low complexity), a sample of 286 adults experiencing acute pain reported their pain intensity and pain unpleasantness pre- and post-music listening. A bespoke piece of music was co-created with a commercial artist to enable the manipulation of music complexity while controlling for familiarity, while facilitating an authentic music listening experience. Overall, findings demonstrated that increased perceived control over music is associated with analgesic benefits, and that perceived choice is more important than music complexity. Highlighting the importance of listener engagement, people who reported higher levels of active engagement experienced greater decreases of pain intensity in the perceived choice condition, than those who reported lower levels of active engagement. These findings have implications for both research and practice, emphasising the importance of facilitating freedom of choice, and sustained engagement with music throughout music listening interventions

How do people with chronic pain choose their music for pain management? Examining the external validity of the cognitive vitality model.

Peer reviewed: TrueAcknowledgements: The authors would like to acknowledge their appreciation for the time and effort invested by patients in the pain management clinic in St. Vincent’s University Hospital. This includes all of the patients that took part in the study, and all those who took time to consider it. We appreciate that participating in research studies can be demanding. Additionally, we would like to thank all of the staff who helped to make this happen, which includes members of the multi-disciplinary pain management team, secretarial staff, and the ethics review board. Finally, we would like to highlight the instrumental role of Chronic Pain Ireland who helped us to promote this study with the wider chronic pain community outside of the hospital setting. We could not have done this project without you.Music interventions for pain are more successful when patients choose the music themselves. But little is known about the attentional strategies used by chronic pain patients when choosing or using music for pain management, and the degree to which these attentional strategies align with the cognitive mechanisms outlines in the cognitive vitality model (CVM, a recently developed theoretical framework that outlines five cognitive mechanisms that mediate the analgesic effects of music for pain management). To investigate this question, we used a sequential explanatory mixed method approach, which included a survey, online music listening experiment, and qualitative data collection, with chronic pain patients (n=70). First, we asked chronic pain patients to name a piece of music that they would use to manage their chronic pain, and answer 19 questions about why they chose that particular piece of music using a questionnaire based on the CVM. Next, we asked chronic pain patients to listen to high energy and low energy pieces of music, to understand aesthetic music preferences and emotional responses at the group level. Finally, participants were asked to qualitatively tell us how they used music to manage their pain. Factor Analysis was completed on the survey data, and identified a five-factor structure in participant responses that was consistent with five mechanisms identified in the CVM. Regression analysis indicated that chronic pain patients choose music for pain management if they think it will facilitate Musical Integration and Cognitive Agency. Musical Integration refers to the degree to which the music can provide an immersive and absorbing experience. Cognitive Agency refers to having an increased feeling of control. At the group level, participants reported a preference for low energy music, and reported that they found high energy music more irritating. However, is it important to note that individual people had different music preferences. Thematic synthesis of patient responses highlighted how these processes mediate the analgesic benefits of music listening from the perspective of chronic pain patients, and highlighted the wide range of music used by participants for chronic pain management including electronic dance music, heavy metal and Beethoven. These findings demonstrate that chronic pain patients use specific attentional strategies when using music for pain management, and these strategies align with the cognitive vitality model

Family and healthcare professionals’ perceptions of a pilot hospice at home programme for children: a qualitative study

Background: Parents commonly report a significant improvement in quality of life following the provision of hospice and supportive care and have identified a need for such a service in the home. The purpose of this study was to understand the experiences of families receiving a nurse led pilot hospice at home programme and the experiences of healthcare professionals delivering and engaging with the programme. Methods: An exploratory, qualitative study was conducted, including telephone interviews with parents and focus groups and individual interviews with healthcare professionals. All parents of families who received the programme of care between June 2014 and September 2015 and healthcare professionals delivering and engaging with the programme were invited to participate. Results: Seven parents participated in telephone interviews. Four focus groups took place, two with external stakeholders (18 participants in total), one with in-patient hospice staff (13 participants) and one with the hospice at home team (8 participants). Two additional interviews took place with individual stakeholders who were unable to attend a scheduled focus group. Themes from interviews with parents focused on the value of having consistent and expert care. The findings from healthcare professionals centred on communication within and across services, education and training and lone working. Conclusions: The pilot hospice at home programme was welcomed by all those who took part in the study. The programme may be improved by enhanced clarification of roles, enhanced access to multi-disciplinary services, greater communication across services and improved information provision to families

The Support Needs and Current Practices of Public Health Nurses in the Republic of Ireland Who Provide Support to Breastfeeding Mothers: A Cross-Sectional Survey.

Peer reviewed: TrueBACKGROUND: Breastfeeding continuation rates are low in Ireland. The Breastfeeding Observation and Assessment Tool (BOAT) was developed to assist public health nurses in assessing breastfeeding challenges; however, little is known of its actual usage, the level of training experienced or desired by public health nurses, or their level of confidence in the support they provide to breastfeeding mothers. RESEARCH AIM: To identify the current practices and support needs of public health nurses who provide breastfeeding support in Ireland. METHOD: An online questionnaire was devised to collect respondents' confidence with breastfeeding issues, caseload, and practices. It was distributed to public health nurses with a current child health caseload in one Community Healthcare Organization. Mann Whitney U tests were used to ascertain the relationship between public health nurses' confidence level and those with qualifications in midwifery or as an International Board Certified Lactation Consultant (IBCLC). RESULTS: The survey was completed by 66 public health nurses. Only 14 respondents (21.2%) indicated that they always used the BOAT. The most common reason for not doing so was a lack of education on its use (n = 17, 25.8%). Postholders also certified as IBCLCs were considered by participants to be the most appropriate professionals to resolve certain breastfeeding issues. Confidence levels to manage breastfeeding issues were highest among public health nurses with IBCLC credentialing (U = 12.5, p = .001) while no difference was seen when comparing those with a midwifery degree to those without (U = 184.0, p = .92). Face-to-face workshops and blended-learning approaches were ranked as the preferred formats for breastfeeding education (Median rank = 2). CONCLUSIONS: Breastfeeding education incorporating a face-to-face component is needed to support public health nurses who work with breastfeeding mothers, as is prioritization of recruitment in the community of public health nurses with IBCLC credentials