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

3D Analysis of chromosome architecture: advantages and limitations with SEM

Three-dimensional mitotic plant chromosome architecture can be investigated with the highest resolution with scanning electron microscopy compared to other microscopic techniques at present. Specific chromatin staining techniques making use of simultaneous detection of back-scattered electrons and secondary electrons have provided conclusive information on the distribution of DNA and protein in barley chromosomes through mitosis. Applied to investigate the structural effects of different preparative procedures, these techniques were the groundwork for the ``dynamic matrix model{''} for chromosome condensation, which postulates an energy-dependent process of looping and bunching of chromatin coupled with attachment to a dynamic matrix of associated protein fibers. Data from SEM analysis shows basic higher order chromatin structures: chromomeres and matrix fibers. Visualization of nanogold-labeled phosphorylated histone H3 (ser10) with high resolution on chromomeres shows that functional modifications of chromatin can be located on structural elements in a 3D context. Copyright (C) 2005 S. Karger AG, Basel

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

Effect of electronic adherence monitoring on adherence and outcomes in chronic conditions: A systematic review and metaanalysis

Introduction Electronic adherence monitoring (EAM) is increasingly used to improve adherence. However, there is limited evidence on the effect of EAM in across chronic conditions and on patient acceptability. We aimed to assess the effect of EAM on adherence and clinical outcomes, across all ages and all chronic conditions, and examine acceptability in this systematic review and meta-analysis. Methods A systematic search of Ovid MEDLINE, EMBASE, Social Work Abstracts, PsycINFO, International Pharmaceutical Abstracts and CINAHL databases was performed from database inception to December 31, 2020. Randomised controlled trials (RCTs) that evaluated the effect of EAM on medication adherence as part of an adherence intervention in chronic conditions were included. Study characteristics, differences in adherence and clinical outcomes between intervention and control were extracted from each study. Estimates were pooled using random-effects meta-analysis, and presented as mean differences, standardised mean differences (SMD) or risk ratios depending on the data. Differences by study-level characteristics were estimated using subgroup meta-analysis to identify intervention characteristics associated with improved adherence. Effects on adherence and clinical outcomes which could not be meta-analysed, and patient acceptability, were synthesised narratively. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed, and Risk of bias (RoB) assessed using the Cochrane Collaboration's RoB tool for RCTs. The review is registered with PROSPERO CRD42017084231. Findings Our search identified 365 studies, of which 47 studies involving 6194 patients were included. Data from 27 studies (n = 2584) were extracted for the adherence outcome. The intervention group (n = 1267) had significantly better adherence compared to control (n = 1317), (SMD = 0.93, CI:0.69 to 1.17, p<0.0001) with high heterogeneity across studies (I2 = 86%). There was a significant difference in effect according to intervention complexity (p = 0.01); EAM only improved adherence when used with a reminder and/or health provider support. Clinical outcomes were measured in 38/47 (81%) of studies; of these data from 14 studies were included in a meta-analysis of clinical outcomes for HIV, hypertension and asthma. In total, 13/47 (28%) studies assessed acceptability; patient perceptions were mixed. Interpretation Patients receiving an EAM intervention had significantly better adherence than those who did not, but improved adherence did not consistently translate into clinical benefits. Acceptability data were mixed. Further research measuring effects on clinical outcomes and patient acceptability are needed

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