Regional Growth Rate Differences Specified by Apical Notch Activities Regulate Liverwort Thallus Shape

Plants have undergone 470 million years of evolution on land and different groups have distinct body shapes. Liverworts are the most ancient land plant lineage and have a flattened, creeping body (the thallus), which grows from apical cells in an invaginated "notch." The genetic mechanisms regulating liverwort shape are almost totally unknown, yet they provide a blueprint for the radiation of land plant forms. We have used a combination of live imaging, growth analyses, and computational modeling to determine what regulates liverwort thallus shape in $\textit{Marchantia polymorpha}$. We find that the thallus undergoes a stereotypical sequence of shape transitions during the first 2 weeks of growth and that key aspects of global shape depend on regional growth rate differences generated by the coordinated activities of the apical notches. A "notch-drives-growth" model, in which a diffusible morphogen produced at each notch promotes specified isotropic growth, can reproduce the growth rate distributions that generate thallus shape given growth suppression at the apex. However, in surgical experiments, tissue growth persists following notch excision, showing that this model is insufficient to explain thallus growth. In an alternative "notch-pre-patterns-growth" model, a persistently acting growth regulator whose distribution is pre-patterned by the notches can account for the discrepancies between growth dynamics in the notch-drives-growth model and real plants following excision. Our work shows that growth rate heterogeneity is the primary shape determinant in $\textit{Marchantia polymorpha}$ and suggests that the thallus is likely to have zones with specialized functions.We thank the BBSRC ( BB/F016581/1 ) for funding J.E.S.’s PhD research and the Gatsby Charitable Foundation ( GAT2962 ) and the Royal Society (RG54416) for funding C.J.H.’s research

The changing landscape of professional practice in podiatry, lessons to be learned from other professions about the barriers to change – a narrative review

Background: The delivery of healthcare is changing and aligned with this, the podiatry profession continues to change with evidence informed practice and extending roles. As change is now a constant, this gives clinicians the opportunity to take ownership to drive that change forward. In some cases, practitioners and their teams have done so, where others have been reluctant to embrace change. It is not clear to what extent good practice is being shared, whether interventions to bring about change have been successful, or what barriers exist that have prevented change from occurring. The aim of this article is to explore the barriers to changing professional practice and what lessons podiatry can learn from other health care professions. Main body: A literature search was carried out which informed a narrative review of the findings. Eligible papers had to (1) examine the barriers to change strategies, (2) explore knowledge, attitudes and roles during change interventions, (3) explore how the patients/service users contribute to the change process (4) include studies from predominantly primary care in developed countries. Ninety-two papers were included in the final review. Four papers included change interventions involving podiatrists. The barriers influencing change were synthesised into three themes (1) the organisational context, (2) the awareness, knowledge and attitudes of the professional, (3) the patient as a service user and consumer. Conclusions: Minimal evidence exists about the barriers to changing professional practice in podiatry. However, there is substantial literature on barriers and implementation strategies aimed at changing professional practices in other health professions. Change in practice is often resisted at an organisational, professional or service user level. The limited literature about change in podiatry, a rapidly changing healthcare workforce and the wide range of contexts that podiatrists work, highlights the need to improve the ways in which podiatrists can share successful attempts to change practice

The role of rare codons in protein expression

That the flow of information from gene sequence to protein sequence depends on the translation of a code that could literally be described as digital is a truly incredible feat of nature. However, the process of translation is a noisy, stochastic, kinetic process that depends on many factors. The redundancy in the genetic code allows the transmission of additional, analogue information by varying some of these factors. How organisms use the redundancy is termed codon usage, and rare codons are those that are typically shunned in favour of other synonymous options. Synonymous variations to the codon usage pattern of a gene have been linked to disease, and can have huge effects on the functionality and quantity of protein produced from a gene, but the nature of these variations is complex and poorly understood. In some cases, rare codons appear to have a beneficial influence on expression. This thesis investigates the phenomenon of rare codons and attempts to elucidate their evolutionary role in optimal gene expression. It begins with the design of a novel statistical algorithm, which is used to generate a dataset of interesting genetic locations. The dataset is the subject of a hypothesis-driven investigation to discover meaningful biological correlates, and this is complemented by experimental work, to attempt to provide conclusive validation of the approach

Genetic alterations in lymphoblastic leukaemia / lymphoma – a practical guide to WHO HAEM5

\ua9 2024 the author(s), published by De Gruyter.We present a practical guide for analyzing the genetic aspects of lymphoblastic leukaemia/lymphoma according to the 5th edition of the World Health Organization (WHO) classification of haematolymphoid neoplasms (WHO-HAEM5) issued in 2024. The WHO-HAEM5 acknowledges the increasing importance of genetics in the diagnosis of lymphoid neoplasia. Classification is based on the established genetic subtypes according to cell lineage, with precursor cell neoplasms followed by mature malignancies. This guide describes those genetic abnormalities in acute precursor B- and T-cell neoplasms required for risk stratification, and for treatment, providing diagnostic algorithms under the headings of ‘essential’ and ‘desirable’ diagnostic criteria

Multi-train trajectory optimisation to maximise rail network energy efficiency under travel-time constraints

Optimising the trajectories of multiple interacting trains to maximise energy efficiency is a difficult, but highly desirable, problem to solve. A bespoke genetic algorithm has been developed for the multi-train trajectory optimisation problem and used to seek a near-optimal set of control point distances for multiple trains, such that a weighted sum of the time and energy objectives is minimised. Genetic operators tailored to the problem are developed including a new mutation operation and the insertion and deletion pairs of control points during the reproduction process. Compared with published results, the new GA was shown to increase the quality of solutions found by an average of 27.6% and increase consistency by a factor of 28. This allows more precise control over the relative priority given to achieving time targets or increasing energy efficiency

dup(21q) amplified (RUNX1)

Review on dup(21q) amplified (RUNX1), with data on clinics, and the genes involved

People with Parkinson's Disease: What Symptoms Do They Most Want to Improve and How Does This Change with Disease Duration?

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition with a diverse and complex pattern of motor and non-motor symptoms which change over time with disease duration. OBJECTIVE: The aims of the present study were to discover what symptoms matter most to people with the condition and to examine how these priorities change with disease duration. METHODS: A simple free-text online survey (using SmartSurvey) was developed by Parkinson's UK, which asked participants to identify up to three aspects of the condition they would most like to see improvement in. RESULTS: 790 people participated reporting 2,295 issues related to PD which were grouped into 24 broad symptom domains. Of these, 1,358 (59.1%) were categorised as motor symptoms, 859 (37.4%) as non-motor issues and 78 (3.4%) as medication problems. This study reveals how certain features of PD become more or less important to patients as the condition progresses. Non-motor symptoms were highly cited from the very earliest stages of PD. Problems with walking, balance and falls, speech problems, freezing and dyskinesia become increasingly important as the condition progresses whereas tremor, stiffness and psychological health become decreasingly important as the condition progresses. CONCLUSIONS: The data suggest that the priorities of people affected by PD for improving life are personal and change with duration of the condition. These findings have implications for developing person-centred management and care, as well as for directing future research to improve quality of life

Accelerators as authentic training experiences for nascent entrepreneurs

© 2017, © Emerald Publishing Limited. Purpose: The purpose of this paper is to address the role of accelerators as authentic learning-based entrepreneurial training programs. Accelerators facilitate the development and assessment of entrepreneurial competencies in nascent entrepreneurs through the process of creating a start-up venture. Design/methodology/approach: Survey data from applicants and participants of four start-accelerators are used to explore the linkages between accelerators and the elements of authentic learning. Authentic learning processes are then mapped onto the start-up processes that occur within the accelerators. Findings: Accelerators take in nascent entrepreneurs and work to create start-ups. This activity develops the participants’ entrepreneurial competencies and facilitates authentic self-reflection. Research limitations/implications: This study explores how accelerators can be useful as authentic learning platforms for the development of entrepreneurial competencies. Limitations include perceptual measures and the inability to conduct paired sampling. Practical implications: Entrepreneurship training is studied through the lens of authentic learning activities that occur within an accelerator. Participants develop and assess their mastery of and interest in entrepreneurship through tasks, exposure to experts and mentors, peer learning, and assessments such as pitching to investors at Demo Day. Originality/value: This paper reports on the authentic learning processes and its usefulness in competency development and self-appraisal by accelerators participants. The opportunity for competency development and self-appraisal by nascent entrepreneurs before escalating their commitment to a start-up may be an accelerator’s raison d’être

The Golden Ratio Prediction for the Solar Angle from a Natural Model with A5 Flavour Symmetry

We formulate a consistent model predicting, in the leading order approximation, maximal atmospheric mixing angle, vanishing reactor angle and tan {\theta}_12 = 1/{\phi} where {\phi} is the Golden Ratio. The model is based on the flavour symmetry A5 \times Z5 \times Z3, spontaneously broken by a set of flavon fields. By minimizing the scalar potential of the theory up to the next-to-leading order in the symmetry breaking parameter, we demonstrate that this mixing pattern is naturally achieved in a finite portion of the parameter space, through the vacuum alignment of the flavon fields. The leading order approximation is stable against higher-order corrections. We also compare our construction to other models based on discrete symmetry groups.Comment: 28 pages, 2 figures. Minor changes, references added. Corrected typos in Appendix A. Version appeared on JHE

Changing the culture of assessment: the dominance of the summative assessment paradigm

Background Despite growing evidence of the benefits of including assessment for learning strategies within programmes of assessment, practical implementation of these approaches is often problematical. Organisational culture change is often hindered by personal and collective beliefs which encourage adherence to the existing organisational paradigm. We aimed to explore how these beliefs influenced proposals to redesign a summative assessment culture in order to improve students’ use of assessment-related feedback. Methods Using the principles of participatory design, a mixed group comprising medical students, clinical teachers and senior faculty members was challenged to develop radical solutions to improve the use of post-assessment feedback. Follow-up interviews were conducted with individual members of the group to explore their personal beliefs about the proposed redesign. Data were analysed using a socio-cultural lens. Results Proposed changes were dominated by a shared belief in the primacy of the summative assessment paradigm, which prevented radical redesign solutions from being accepted by group members. Participants’ prior assessment experiences strongly influenced proposals for change. As participants had largely only experienced a summative assessment culture, they found it difficult to conceptualise radical change in the assessment culture. Although all group members participated, students were less successful at persuading the group to adopt their ideas. Faculty members and clinical teachers often used indirect techniques to close down discussions. The strength of individual beliefs became more apparent in the follow-up interviews. Conclusions Naïve epistemologies and prior personal experiences were influential in the assessment redesign but were usually not expressed explicitly in a group setting, perhaps because of cultural conventions of politeness. In order to successfully implement a change in assessment culture, firmly-held intuitive beliefs about summative assessment will need to be clearly understood as a first step