Hypermethylation and small RNA expression are associated with increased age in almond (Prunus dulcis [Mill.] D.A. Webb) accessions.

The focus of this study is to profile changes in DNA methylation and small RNA expression occurring with increased age in almond breeding germplasm to identify possible biomarkers of age that can be used to assess the potential of individuals to develop aging-related disorders. To profile DNA methylation in almond germplasm, 70 methylomes were generated from almond individuals representing three age cohorts (11, 7, and 2 years old) using an enzymatic methyl-seq approach followed by analysis to call differentially methylated regions (DMRs) within these cohorts. Small RNA (sRNA) expression was profiled in three breeding selections, each from two age cohorts (1 and 6 years old), using sRNA-Seq followed by differential expression analysis. Weighted chromosome-level methylation analysis reveals hypermethylation in 11-year-old almond breeding selections when compared to 2-year-old selections in the CG and CHH contexts. Seventeen consensus DMRs were identified in all age contrasts. sRNA expression differed significantly between the two age cohorts tested, with significantly decreased expression in sRNAs in the 6-year-old selections compared to the 1-year-old. Almond shows a pattern of hypermethylation and decreased sRNA expression with increased age. Identified DMRs and differentially expressed sRNAs could function as putative biomarkers of age following validation in additional age groups.

'It's a gamble': A phenomenological exploration of medical students' learning experiences as newcomers to clinical communities of practice.

BACKGROUND: Medical students become members of the clinical team through participation in their activities, as described by Lave and Wenger's situated learning theory. While there is research into how medical students cognitively engage in clinical learning, there is limited work on clinical experiences using a social theoretical lens such as situated learning theory. METHOD: This study explored third year medical students' lived experience as newcomers to clinical teams using a qualitative phenomenological approach. Medical students completed in-depth, semi-structured interviews in 2021. Interpretive phenomenological analysis (IPA) using Lave and Wenger's theory of situated learning was applied to understand students' experiences. RESULTS: Seven students discussed their variable placement experiences. Learning related to three elements: conditions for participation, modes of participation and products of participation. When certain conditions were met relating to student, clinician and activity, students learned. This drove identity and relationship formation. The findings related and led to a self-perpetuating cycle with potential to advance student learning. When the conditions for participation were not met, the cycle stopped, leading to student disengagement. CONCLUSION: Passivity in students is a result of modifiable factors in the workplace. To encourage proactivity, clinicians must enable students to move from observation to participation as their competence increases. Participation should be supervised, challenging and should contribute to patient care. Time pressures can make this difficult; one solution is to nominate a clinician to direct students and account for this in their workload or to employ a clinical fellow to assist with student training.

A review of plant epigenetics through the lens of almond.

While genomes were originally seen as static entities that stably held and organized genetic information, recent advances in sequencing have uncovered the dynamic nature of the genome. New conceptualizations of the genome include complex relationships between the environment and gene expression that must be maintained, regulated, and sometimes even transmitted over generations. The discovery of epigenetic mechanisms has allowed researchers to understand how traits like phenology, plasticity, and fitness can be altered without changing the underlying deoxyribonucleic acid sequence. While many discoveries were first made in animal systems, plants provide a particularly complex set of epigenetic mechanisms due to unique aspects of their biology and interactions with human selective breeding and cultivation. In the plant kingdom, annual plants have received the most attention; however, perennial plants endure and respond to their environment and human management in distinct ways. Perennials include crops such as almond, for which epigenetic effects have long been linked to phenomena and even considered relevant for breeding. Recent discoveries have elucidated epigenetic phenomena that influence traits such as dormancy and self-compatibility, as well as disorders like noninfectious bud failure, which are known to be triggered by the environment and influenced by inherent aspects of the plant. Thus, epigenetics represents fertile ground to further understand almond biology and production and optimize its breeding. Here, we provide our current understanding of epigenetic regulation in plants and use almond as an example of how advances in epigenetics research can be used to understand biological fitness and agricultural performance in crop plants.

A theoretical systematic review of patient involvement in health and social care education.

Patient involvement in health and social care education lacks theoretical underpinning, despite increasing calls for rigour. Theories help explain how learning is advanced and offer guidance for how faculty work with patients who become involved in curriculum delivery. We conducted a systematic review to synthesise how theory shapes our understanding of patient involvement in health and social care education. Three databases were systematically searched. Studies demonstrating explicit and high-quality application of theory to patient involvement in teaching and learning or involvement within a community of health and social care educators, were included. A narrative synthesis was undertaken using Activity Theory as an analytical lens to highlight the multifaceted components of patient involvement in professional education. Seven high-quality, theoretically underpinned studies were included. Four studies applied theory to pedagogy, showing how deep learning from patient involvement occurred. Despite a growing body of studies which attempt to use theory to explain learning, many were descriptive, lacked theoretical quality and were therefore excluded. Three studies applied theory to illuminate the complexity of involving patients in the educational system, showing how patients can be supported and valued in teaching roles. This review highlights that more work is required to identify the mechanisms through which patient involvement enhances learning and, to explore what involvement within the education community means for faculty and patients. Our understandings of patient-educator partnerships for learning could be progressed by further high-quality theory driven studies, which include the patient voice.

Identification of Putative Markers of Non-infectious Bud Failure in Almond [Prunus dulcis (Mill.) D.A. Webb] Through Genome Wide DNA Methylation Profiling and Gene Expression Analysis in an Almond × Peach Hybrid Population.

Almond [Prunus dulcis (Mill.) D.A. Webb] is an economically important nut crop susceptible to the genetic disorder, Non-infectious Bud Failure (NBF). Despite the severity of exhibition in several prominent almond cultivars, no causal mechanism has been identified underlying NBF development. The disorder is hypothesized to be associated with differential DNA methylation patterns based on patterns of inheritance (i.e., via sexual reproduction and clonal propagation) and previous work profiling methylation in affected trees. Peach (Prunus persica L. Batsch) is a closely related species that readily hybridizes with almond; however, peach is not known to exhibit NBF. A cross between an NBF-exhibiting 'Carmel' cultivar and early flowering peach ('40A17') produced an F1 where ∼50% of progeny showed signs of NBF, including canopy die-back, erratic branching patterns (known as "crazy-top"), and rough bark. In this study, whole-genome DNA methylation profiles were generated for three F1 progenies exhibiting NBF and three progenies considered NBF-free. Subsequent alignment to both the almond and peach reference genomes showed an increase in genome-wide methylation levels in NBF hybrids in CG and CHG contexts compared to no-NBF hybrids when aligned to the almond genome but no difference in methylation levels when aligned to the peach genome. Significantly differentially methylated regions (DMRs) were identified by comparing methylation levels across the genome between NBF- and no-NBF hybrids in each methylation context. In total, 115,635 DMRs were identified based on alignment to the almond reference genome, and 126,800 DMRs were identified based on alignment to the peach reference genome. Nearby genes were identified as associated with the 39 most significant DMRs occurring either in the almond or peach alignments alone or occurring in both the almond and peach alignments. These DMR-associated genes include several uncharacterized proteins and transposable elements. Quantitative PCR was also performed to analyze the gene expression patterns of these identified gene targets to determine patterns of differential expression associated with differential DNA methylation. These DMR-associated genes, particularly those showing corresponding patterns of differential gene expression, represent key targets for almond breeding for future cultivars and mitigating the effects of NBF-exhibition in currently affected cultivars.

Relative Telomere Length and Telomerase Reverse Transcriptase (TERT) Expression Are Associated with Age in Almond (Prunus dulcis [Mill.] D.A.Webb).

While all organisms age, our understanding of how aging occurs varies among species. The aging process in perennial plants is not well-defined, yet can have implications on production and yield of valuable fruit and nut crops. Almond exhibits an age-related disorder known as non-infectious bud failure (BF) that affects vegetative bud development, indirectly affecting kernel yield. This species and disorder present an opportunity to address aging in a commercially relevant and vegetatively propagated perennial crop. The hypothesis tested in this study was that relative telomere length and/or telomerase reverse transcriptase (TERT) expression can serve as biomarkers of aging in almond. Relative telomere lengths and expression of TERT, a subunit of the enzyme telomerase, were measured via qPCR methods using bud and leaf samples collected from distinct age cohorts over a two-year period. Results from this work show a marginal but significant association between both relative telomere length and TERT expression, and age, suggesting that as almonds age, telomeres shorten and TERT expression decreases. This work provides information on potential biomarkers of perennial plant aging, contributing to our knowledge of this process. In addition, these results provide opportunities to address BF in almond breeding and nursery propagation.

Surgeon-Team Separation in Robotic Theaters: A Qualitative Observational and Interview Study.

BACKGROUND: The rapid uptake of robotic surgery has largely been driven by the improved technical aspects of minimally invasive surgery including improved ergonomics, wristed instruments, and 3-dimensional vision. However, little attention has been given to the effect of physical separation of the surgeon from the rest of the operating team. PURPOSE: The aim of this study was to examine in depth how this separation affected team dynamics and staff emotions. METHODS: Robotic procedures were observed in 2 tertiary hospitals, and laparoscopic/open procedures were added for comparison; field notes were taken instantaneously. One-to-one interviews with theater team members were audio recorded and transcribed verbatim. Qualitative analysis was conducted via grounded theory approach using NVIVO11. RESULTS: Twenty-nine participants (26 interviewed) were recruited to the study (11 females) and 134 (109 robotic) hours of observation were completed across gynecology, urology, and colorectal surgery.The following 3 main themes emerged with compounding factors identified: (a) communication challenge, (b) immersion versus distraction, and (c) emotional impact. Compounding factors included the following: individual and team experience, staffing levels, and the physical theater environment. CONCLUSIONS: Our emergent theory is that "surgeon-team separation in robotic theaters poses communication challenges which impacts on situational awareness and staff emotions." These can be ameliorated by staff training, increased experience, and team/procedure consistency.

Academic ability and teamworking in medical students.

BACKGROUND: Teamworking is an essential skill for a doctor to develop in order to work effectively, and is required in the UK as part of the General Medical Council (GMC) Good Medical Practice guidance. Assessment of teamwork may be difficult, however, with medical school assessments being more commonly focused on knowledge and individual skills. We aim to explore the link between academic ability as measured at final medical examinations and teamworking. METHODS: All final-year medical students were asked to attend a simulation session in an immersive 22-bed simulated ward, which used a combination of patient simulators and high-fidelity manikin simulators, with nursing and telephone support. Students were split into separate groups stratified by performance in final-year assessments or in groups with mixed performance. Students were observed in real time by faculty staff and assessed with the individual Teamwork Observation and Feedback Tool (iTOFT), around which the debriefing was centred. Assessment of teamwork may be difficult RESULTS: The performance of 119 students in simulation was assessed, and groups with a mix of academic performance showed significantly greater teamworking ability as measured with the iTOFT as compared with those stratified by performance (p = 0.045). Final assessment at medical school was shown to be a poor predictor of teamworking ability: those who performed best at assessment seemed to underperform in teamworking. DISCUSSION: The simulated-ward learning activity received positive feedback, although the mix of patient simulators and high-fidelity manikins proved a challenge to some students. Medical school assessments appear to be inadequate in the assessment of teamworking ability, with change needed in future to ensure that this and other non-technical skills are assessed.

Perspectives on patients and carers in leading teaching roles in interprofessional education.

The involvement of patients and carers is central to the values of interprofessional education (IPE) which aims to improve the experience of care and care delivery. Partnership arrangements with service users and carers within Higher Education Institutions face the same barriers relating to status, power, and resources, as the implementation of IPE. The complexity of these alignments can be explained by Activity Theory (AT). Using a qualitative research methodology we set out to consider the stakeholder perspectives on whether patients should progress from telling their stories to taking on a leading teaching role, within a well-established IPE workshop. Following the principles of Participatory Action Research, data were collected cyclically, using consultation meetings, interviews (with tutors and patients) and focus groups (with students). The work was overseen by a steering group who reviewed and clarified the analysis, informed by AT. All stakeholders endorsed the validity of patients as teachers. Two new leadership roles were proposed; patients as Co-Tutors and as Mentors supporting the workshop. Service users and carers were realistic about the support required for progression. Students were more ambivalent, recognizing the right of patients to tell their stories but having concerns about their competence and potential bias when in leading roles. There is overall support for the development of a progressive route for patients to move beyond telling stories into leading teaching roles in IPE, but this brings added complexity and requires a supportive infrastructure, careful preparation of students and further research.

Patient safety and interprofessional education: A report of key issues from two interprofessional workshops.

This article presents the outcomes of two workshops which explored historical and recent issues on patient safety that directly relate to leaders in the interprofessional field. The article considers the impact of flattened team-based structures where collaborative working constantly considers safe patient-centred high-quality care. These issues are mainly rooted in changes within a UK context, but the historical case studies present situations which could enlighten and enliven discussions of patient safety in an international context. The article was sparked by discussion of recurrent themes in healthcare that have undermined the abilities of medical practitioners to adequately manage hazard in clinical care settings throughout modern history. Examining the issues that confront healthcare practitioners and care workers in their dealings with patients and clients, such as the aged or the severely disabled, can reveal commonalities across global healthcare settings, in the past and present, that provide a useful tool in facilitating the goals of interprofessional education (IPE). The potential of IPE has links to both how professionals respond together to care situations and involve the general public in shared health understandings. The outcomes focus on how to ensure ministrations where optimal team-based collaborative care is recognised and constantly sought. We conclude that IPE has much to offer in this arena and more evidence of impact here is well worth pursuing.

International consensus statement on the assessment of interprofessional learning outcomes.

Regulatory frameworks around the world mandate that health and social care professional education programs graduate practitioners who have the competence and capability to practice effectively in interprofessional collaborative teams. Academic institutions are responding by offering interprofessional education (IPE); however, there is as yet no consensus regarding optimal strategies for the assessment of interprofessional learning (IPL). The Program Committee for the 17th Ottawa Conference in Perth, Australia in March, 2016, invited IPE champions to debate and discuss the current status of the assessment of IPL. A draft statement from this workshop was further discussed at the global All Together Better Health VIII conference in Oxford, UK in September, 2016. The outcomes of these deliberations and a final round of electronic consultation informed the work of a core group of international IPE leaders to develop this document. The consensus statement we present here is the result of the synthesized views of experts and global colleagues. It outlines the challenges and difficulties but endorses a set of desired learning outcome categories and methods of assessment that can be adapted to individual contexts and resources. The points of consensus focus on pre-qualification (pre-licensure) health professional students but may be transferable into post-qualification arenas.

Clinical evaluation of music perception, appraisal and experience in cochlear implant users.

OBJECTIVES: The objectives were to evaluate the relationships among music perception, appraisal, and experience in cochlear implant users in multiple clinical settings and to examine the viability of two assessments designed for clinical use. DESIGN: Background questionnaires (IMBQ) were administered by audiologists in 14 clinics in the United States and Canada. The CAMP included tests of pitch-direction discrimination, and melody and timbre recognition. The IMBQ queried users on prior musical involvement, music listening habits pre and post implant, and music appraisals. STUDY SAMPLE: One-hundred forty-five users of Advanced Bionics and Cochlear Ltd cochlear implants. RESULTS: Performance on pitch direction discrimination, melody recognition, and timbre recognition tests were consistent with previous studies with smaller cohorts, as well as with more extensive protocols conducted in other centers. Relationships between perceptual accuracy and music enjoyment were weak, suggesting that perception and appraisal are relatively independent for CI users. CONCLUSIONS: Perceptual abilities as measured by the CAMP had little to no relationship with music appraisals and little relationship with musical experience. The CAMP and IMBQ are feasible for routine clinical use, providing results consistent with previous thorough laboratory-based investigations.

Can unaided non-linguistic measures predict cochlear implant candidacy?

OBJECTIVE: To determine if unaided, non-linguistic psychoacoustic measures can be effective in evaluating cochlear implant (CI) candidacy. STUDY DESIGN: Prospective split-cohort study including predictor development subgroup and independent predictor validation subgroup. SETTING: Tertiary referral center. SUBJECTS: Fifteen subjects (28 ears) with hearing loss were recruited from patients visiting the University of Washington Medical Center for CI evaluation. METHODS: Spectral-ripple discrimination (using a 13-dB modulation depth) and temporal modulation detection using 10- and 100-Hz modulation frequencies were assessed with stimuli presented through insert earphones. Correlations between performance for psychoacoustic tasks and speech perception tasks were assessed. Receiver operating characteristic curve analysis was performed to estimate the optimal psychoacoustic score for CI candidacy evaluation in the development subgroup and then tested in an independent sample. RESULTS: Strong correlations were observed between spectral-ripple thresholds and both aided sentence recognition and unaided word recognition. Weaker relationships were found between temporal modulation detection and speech tests. Receiver operating characteristic curve analysis demonstrated that the unaided spectral-ripple discrimination shows a good sensitivity, specificity, positive predictive value, and negative predictive value compared to the current gold standard, aided sentence recognition. CONCLUSION: Results demonstrated that the unaided spectral-ripple discrimination test could be a promising tool for evaluating CI candidacy.

A demonstration of improved precision of word recognition scores.

PURPOSE The purpose of this study was to demonstrate improved precision of word recognition scores (WRSs) by increasing list length and analyzing phonemic errors. METHOD Pure-tone thresholds (frequencies between 0.25 and 8.0 kHz) and WRSs were measured in 3 levels of speech-shaped noise (50, 52, and 54 dB HL) for 24 listeners with normal hearing. WRSs were obtained for half-lists and full lists of Northwestern University Test No. 6 (Tillman & Carhart, 1966) words presented at 48 dB HL. A resampling procedure was used to derive dimensionless effect sizes for identifying a change in hearing using the data. This allowed the direct comparison of the magnitude of shifts in WRS (%) and in the average pure-tone threshold (dB), which provided a context for interpreting the WRS. RESULTS WRSs based on a 50-word list analyzed by the percentage of correct phonemes were significantly more sensitive for identifying a change in hearing than the WRSs based on 25-word lists analyzed by percentage of correct words. CONCLUSION Increasing the number of items that contribute to a WRS significantly increased the test's ability to identify a change in hearing. Clinical and research applications could potentially benefit from a more precise word recognition test, the only basic audiologic measure that estimates directly the distortion component of hearing loss and its effect on communication.

Validation of a clinical assessment of spectral-ripple resolution for cochlear implant users.

OBJECTIVES: Nonspeech psychophysical tests of spectral resolution, such as the spectral-ripple discrimination task, have been shown to correlate with speech-recognition performance in cochlear implant (CI) users. However, these tests are best suited for use in the research laboratory setting and are impractical for clinical use. A test of spectral resolution that is quicker and could more easily be implemented in the clinical setting has been developed. The objectives of this study were (1) To determine whether this new clinical ripple test would yield individual results equivalent to the longer, adaptive version of the ripple-discrimination test; (2) To evaluate test-retest reliability for the clinical ripple measure; and (3) To examine the relationship between clinical ripple performance and monosyllabic word recognition in quiet for a group of CI listeners. DESIGN: Twenty-eight CI recipients participated in the study. Each subject was tested on both the adaptive and the clinical versions of spectral ripple discrimination, as well as consonant-nucleus-consonant word recognition in quiet. The adaptive version of spectral ripple used a two-up, one-down procedure for determining spectral ripple discrimination threshold. The clinical ripple test used a method of constant stimuli, with trials for each of 12 fixed ripple densities occurring six times in random order. Results from the clinical ripple test (proportion correct) were then compared with ripple-discrimination thresholds (in ripples per octave) from the adaptive test. RESULTS: The clinical ripple test showed strong concurrent validity, evidenced by a good correlation between clinical ripple and adaptive ripple results (r = 0.79), as well as a correlation with word recognition (r = 0.7). Excellent test-retest reliability was also demonstrated with a high test-retest correlation (r = 0.9). CONCLUSIONS: The clinical ripple test is a reliable nonlinguistic measure of spectral resolution, optimized for use with CI users in a clinical setting. The test might be useful as a diagnostic tool or as a possible surrogate outcome measure for evaluating treatment effects in hearing.

Assessing the role of spectral and intensity cues in spectral ripple detection and discrimination in cochlear-implant users.

Measures of spectral ripple resolution have become widely used psychophysical tools for assessing spectral resolution in cochlear-implant (CI) listeners. The objective of this study was to compare spectral ripple discrimination and detection in the same group of CI listeners. Ripple detection thresholds were measured over a range of ripple frequencies and were compared to spectral ripple discrimination thresholds previously obtained from the same CI listeners. The data showed that performance on the two measures was correlated, but that individual subjects' thresholds (at a constant spectral modulation depth) for the two tasks were not equivalent. In addition, spectral ripple detection was often found to be possible at higher rates than expected based on the available spectral cues, making it likely that temporal-envelope cues played a role at higher ripple rates. Finally, spectral ripple detection thresholds were compared to previously obtained speech-perception measures. Results confirmed earlier reports of a robust relationship between detection of widely spaced ripples and measures of speech recognition. In contrast, intensity difference limens for broadband noise did not correlate with spectral ripple detection measures, suggesting a dissociation between the ability to detect small changes in intensity across frequency and across time.

Placing interprofessional learning at the heart of improving practice: the activities and achievements of CLAHRC in Leicestershire, Northamptonshire and Rutland.

BACKGROUND: The National Institute for Health Research initiative 'collaborations for leadership in applied health research and care' (CLAHRC) in Leicestershire Northamptonshire and Rutland (LNR) is a partnership between the University of Leicester and NHS trusts in LNR that aims to reduce the second gap in translation (the long delay between conducting research and it having an impact on clinical practice). METHOD: CLAHRC-LNR appointed specialist staff as boundary spanners and knowledge brokers to improve links between academia and the NHS, and to facilitate a range of activities designed to increase the implementation of research evidence. An interprofessional and interdisciplinary approach is used and incorporates a range of activities including: applied research, service evaluation and pilot projects, education and training events, knowledge dissemination activities and developing networks to increase the use of research in the NHS partners. RESULTS: CLAHRC-LNR's close collaboration with partner NHS trusts has aided the development of a programme of applied research that aims to develop interprofessional teamworking to improve healthcare systems and patient outcomes. Co-ordinators (boundary spanners) have been appointed in trusts and have been crucial in facilitating interprofessional working. Activities include a successful programme of training and education courses within the NHS partner trusts using the principles of interprofessional education. CLAHRC-LNR is developing the use of knowledge exchange events and workshops as well as establishing communities of practice to bring together professionals from across LNR NHS trusts and the University of Leicester to share their expertise and build interprofessional relationships. CLAHRC fellows (knowledge brokers) are being appointed to work with co-ordinators to facilitate the use of research evidence in decision making in the trusts and clinical commissioning groups (CCGs). CONCLUSION: Interprofessional working is integral to the approach adopted by CLAHRC-LNR, running through many of its activities, and is proving vital to addressing and helping to close the second gap in translation.

Comparing spatial tuning curves, spectral ripple resolution, and speech perception in cochlear implant users.

Spectral ripple discrimination thresholds were measured in 15 cochlear-implant users with broadband (350-5600 Hz) and octave-band noise stimuli. The results were compared with spatial tuning curve (STC) bandwidths previously obtained from the same subjects. Spatial tuning curve bandwidths did not correlate significantly with broadband spectral ripple discrimination thresholds but did correlate significantly with ripple discrimination thresholds when the rippled noise was confined to an octave-wide passband, centered on the STC's probe electrode frequency allocation. Ripple discrimination thresholds were also measured for octave-band stimuli in four contiguous octaves, with center frequencies from 500 Hz to 4000 Hz. Substantial variations in thresholds with center frequency were found in individuals, but no general trends of increasing or decreasing resolution from apex to base were observed in the pooled data. Neither ripple nor STC measures correlated consistently with speech measures in noise and quiet in the sample of subjects in this study. Overall, the results suggest that spectral ripple discrimination measures provide a reasonable measure of spectral resolution that correlates well with more direct, but more time-consuming, measures of spectral resolution, but that such measures do not always provide a clear and robust predictor of performance in speech perception tasks.