Dev-ResNet: automated developmental event detection using deep learning.

Delineating developmental events is central to experimental research using early life stages, permitting widespread identification of changes in event timing between species and environments. Yet, identifying developmental events is incredibly challenging, limiting the scale, reproducibility and throughput of using early life stages in experimental biology. We introduce Dev-ResNet, a small and efficient 3D convolutional neural network capable of detecting developmental events characterised by both spatial and temporal features, such as the onset of cardiac function and radula activity. We demonstrate the efficacy of Dev-ResNet using 10 diverse functional events throughout the embryonic development of the great pond snail, Lymnaea stagnalis. Dev-ResNet was highly effective in detecting the onset of all events, including the identification of thermally induced decoupling of event timings. Dev-ResNet has broad applicability given the ubiquity of bioimaging in developmental biology, and the transferability of deep learning, and so we provide comprehensive scripts and documentation for applying Dev-ResNet to different biological systems.

Professional identity and GP trainers as educational leaders.

GP training in the UK has a long history of success, however that is measured. That success is in part due to the formality and credentialling that underlies preparation to take on that role of a GP teacher, which is somewhat under current threat due to workforce pressures. We identify three important factors associated with the GP trainer function [leadership, professional identity and clinical care improvement] that are not often analysed but are at some risk if preparation for the GP trainer role is reduced or devalued. Of particular note are the differing ways that GPs conceptualise their professional roles as teachers and clinicians, despite the transferable skills between them, the demonstrably improved patient care that occurs in practices that teach, and the necessary connections between educational theory and practice. We suggest that these areas define a research agenda ripe for exploration.

The impact of communication training on the clinical care of hypertension in general practice: a cluster randomized controlled trial in China.

BACKGROUND: Hypertension is one of the most common chronic diseases with a low control rate globally. The effect of communication skills training contributing to hypertension control remains uncertain. The aim of the present study was to assess the effectiveness of an educational intervention based on the Calgary-Cambridge guide in improving hypertensive management. METHODS: A cluster randomized controlled trial enrolled 27 general practitioners (GPs) and 540 uncontrolled hypertensive patients attending 6 community health centers in Chengdu, China. GPs allocated to the intervention group were trained by an online communication course and two face-to-face workshops based on Calgary-Cambridge guides. The primary outcome was blood pressure (BP) control rates and reductions in systolic and diastolic BP from baseline to 3 months. The secondary outcome was changes in GPs' communication skills after one month, patients' knowledge and satisfaction after 3 months. Bivariate analysis and the regression model assessed whether the health provider training improved outcomes. RESULTS: After the communication training, the BP control rate was significantly higher (57.2% vs. 37.4%, p < 0.001) in the intervention groups. Compared to the control group, there was a significant improvement in GP's communication skills (13.0 vs 17.5, p < 0.001), hypertensive patients' knowledge (18.0 vs 20.0, p < 0.001), and systolic blood pressure (139.1 vs 134.7, p < 0.001) after 3 months of follow-up. Random effects least squares regression models showed significant interactions between the intervention group and time period in the change of GP's communication skills (Parameter Estimated (PE): 0.612, CI:0.310,0.907, p = 0.006), hypertensive patient's knowledge (PE:0.233, CI: 0.098, 0.514, p < 0.001), satisfaction (PE:0.495, CI: 0.116, 0.706, p = 0.004), SBP (PE:-0.803, CI: -1.327, -0.389, p < 0.001) and DBP (PE:-0.918, CI: -1.694, -0.634, p < 0.001), from baseline to follow-up. CONCLUSION: Communication training based on the Calgary-Cambridge guide for GPs has shown to be an efficient way in the short term to improve patient-provider communication skills and hypertension outcomes among patients with uncontrolled BPs. TRIAL REGISTRATION: The trial was registered on Chinese Clinical Trials Registry on 2019-04-03. (ChiCTR1900022278).

Exposure to digital vape marketing among young people in Aotearoa New Zealand.

AIMS: Little is known about the exposure of young people in Aotearoa New Zealand to marketing of vape products on social media. This study investigated vaping behaviour and the extent of vape marketing exposure and engagement that young people (14-20 years) report on social media and examined differences across socio-demographic groups. METHODS: An online survey was conducted with 3,698 participants aged between 14-20 years (M=17.1; SD=1.8). A range of genders (55.7% females, 38.3% males and 6% another gender), ethnicities (25.6% Maori, 46.7% Pakeha or NZ European, 6.5% Pasifika and 21.2% another ethnicity) and social classes took part. RESULTS: Half (50.8%; n=1,110) of the respondents (N=2,185) reported that they had vaped at least once; vaping history was positively related to exposure to and engagement with digital vape marketing. Half (50.3%; n=1,119) of the respondents (N=2,224) reported seeing vape marketing on at least one social media platform. Binary logistic regressions showed that younger respondents were more likely to report seeing vape marketing than older respondents, and Maori and Pasifika more likely than other ethnicities. Over a quarter (26%; n=563) of respondents (N=2,148) reported engaging with vape marketing online, with Maori and Pasifika respondents more likely to engage than other ethnicity groups, and similarly for respondents of lower compared to higher socio-economic status. No interaction effects were found. CONCLUSIONS: Many young people, including a subset under the legal age for purchase, reported seeing vape product marketing on social media platforms. Patterns of exposure to vape product marketing on social media mirror the inequitable marketing exposure of harmful commodities in physical environments. Improved transparency and regulation of social media marketing is required.

Medical ethics education as translational bioethics.

We suggest that in the particular context of medical education, ethics can be considered in a similar way to other kinds of knowledge that are categorised and shaped by academics in the context of wider society. Moreover, the study of medical ethics education is translational in a manner loosely analogous to the study of medical education as adjunct to translational medicine. Some have suggested there is merit in the idea that much as translational research attempts to connect the laboratory scientist's work to its implications for patient care, translational ethics focuses on bringing ethics scholarship into the sphere of personal and public action. We distinguish the term 'translational ethics' (the study of ethics being translated between academy, classroom and clinic) from other prominent definitions in the bioethics literature. To do this, we build off a notion of knowledge translation that focuses on the nonlinear movement of information that comes to professionals through multiple competing sources. We suggest that this knowledge, and particularly knowledge about ethics, becomes embodied by the individual. It is through a reflective practice that internally embedded ethics knowledge might be modified, and this work might be best carried out with a moral community that maintains a sense of practical wisdom. Applying this translational approach to the study of medical ethics education can be both academically relevant and practically useful. This view of translation can help bridge the evident, multidirectional relationships between research, education and performance. It might also create further opportunities to develop medical ethics education theory.

The embryonic thermal environment has positive but weak effects on thermal tolerance later in life in the aquatic invertebrate Gammarus chevreuxi.

Recent evidence suggests that the adult phenotype is influenced by temperatures experienced in early life. However, our understanding of the extent to which the embryonic environment can modulate thermal tolerance later in life is limited, owing to the paucity of studies with appropriate experimental designs to test for this form of developmental plasticity. We investigated whether the thermal environment experienced during embryonic development affects thermal limits in later life. Embryos of the estuarine amphipod Gammarus chevreuxi were incubated until hatching to 15 °C, 20 °C and 25 °C, then reared under a common temperature. Using thermal ramping assays, we determined upper thermal limits in juveniles, four weeks post-hatch. Individuals exposed to higher temperatures during embryonic development displayed greater thermal tolerance as juveniles (acclimation response ratio ≈ 0.10-0.25 for upper lethal temperature). However, we suggest that the degree of developmental plasticity observed is limited, and will provide little benefit under future climate change scenarios.

The north-south divide? Macroalgal functional trait diversity and redundancy varies with intertidal aspect.

BACKGROUND AND AIMS: Marine macroalgae ('seaweeds') are critical to coastal ecosystem structure and function, but also vulnerable to the many environmental changes associated with anthropogenic climate change (ACC). The local habitat conditions underpinning observed and predicted ACC-driven changes in intertidal macroalgal communities are complex and probably site-specific and operate in addition to more commonly reported regional factors such as sea surface temperatures. METHODS: We examined how the composition and functional trait expression of macroalgal communities in SW England varied with aspect (i.e. north-south orientation) at four sites with opposing Equator- (EF) and Pole-facing (PF) surfaces. Previous work at these sites had established that average annual (low tide) temperatures vary by 1.6 °C and that EF-surfaces experience six-fold more frequent extremes (i.e. >30 °C). KEY RESULTS: PF macroalgal communities were consistently more taxon rich; 11 taxa were unique to PF habitats, with only one restricted to EF. Likewise, functional richness and dispersion were greater on PF-surfaces (dominated by algae with traits linked to rapid resource capture and utilization, but low desiccation tolerance), although differences in both taxon and functional richness were probably driven by the fact that less diverse EF-surfaces were dominated by desiccation-tolerant fucoids. CONCLUSIONS: Although we cannot disentangle the influence of temperature variation on algal ecophysiology from the indirect effects of aspect on species interactions (niche pre-emption, competition, grazing, etc.), our study system provides an excellent model for understanding how environmental variation at local scales affects community composition and functioning. By virtue of enhanced taxonomic diversity, PF-aspects supported higher functional diversity and, consequently, greater effective functional redundancy. These differences may imbue PF-aspects with resilience against environmental perturbation, but if predicted increases in global temperatures are realized, some PF-sites may shift to a depauperate, desiccation-tolerant seaweed community with a concomitant loss of functional diversity and redundancy.

Comparative phenomics: a new approach to study heterochrony.

Understanding the links between development and evolution is one of the major challenges of biology. 'Heterochronies', evolutionary alterations in the timings of development are posited as a key mechanism of evolutionary change, but their quantification requires gross simplification of organismal development. Consequently, how changes in event timings influence development more broadly is poorly understood. Here, we measure organismal development as spectra of energy in pixel values of video, creating high-dimensional landscapes integrating development of all visible form and function. This approach we termed 'Energy proxy traits' (EPTs) is applied alongside previously identified heterochronies in three freshwater pulmonate molluscs (Lymnaea stagnalis, Radix balthica and Physella acuta). EPTs were calculated from time-lapse video of embryonic development to construct a continuous functional time series. High-dimensional transitions in phenotype aligned with major sequence heterochronies between species. Furthermore, differences in event timings between conspecifics were associated with changes in high-dimensional phenotypic space. We reveal EPTs as a powerful approach to considering the evolutionary importance of alterations to developmental event timings. Reimagining the phenotype as energy spectra enabled continuous quantification of developmental changes in high-dimensional phenotypic space, rather than measurement of timings of discrete events. This approach has the possibility to transform how we study heterochrony and development more generally.

Relational care and epistemic injustice.

The philosophical underpinnings of primary care have been examined from several perspectives in recent years. In two previous articles, we have argued that a relational view of autonomy is better matched to the primary care setting than others, and that view is mainly formed from the descriptors of its practice. Here we develop that analysis further, linking it to other relevant theory: the experience of human suffering and epistemic injustice. We argue that relational care is fundamental to ameliorating epistemic injustice and that relationships are integral to ethical practice, rather than being distinct. We propose that personalised care as described in the NHS Long Term Plan is not possible without addressing epistemic injustice and therefore without reconsidering our existing normative ethical frameworks.

Phenomics as an approach to Comparative Developmental Physiology.

The dynamic nature of developing organisms and how they function presents both opportunity and challenge to researchers, with significant advances in understanding possible by adopting innovative approaches to their empirical study. The information content of the phenotype during organismal development is arguably greater than at any other life stage, incorporating change at a broad range of temporal, spatial and functional scales and is of broad relevance to a plethora of research questions. Yet, effectively measuring organismal development, and the ontogeny of physiological regulations and functions, and their responses to the environment, remains a significant challenge. "Phenomics", a global approach to the acquisition of phenotypic data at the scale of the whole organism, is uniquely suited as an approach. In this perspective, we explore the synergies between phenomics and Comparative Developmental Physiology (CDP), a discipline of increasing relevance to understanding sensitivity to drivers of global change. We then identify how organismal development itself provides an excellent model for pushing the boundaries of phenomics, given its inherent complexity, comparably smaller size, relative to adult stages, and the applicability of embryonic development to a broad suite of research questions using a diversity of species. Collection, analysis and interpretation of whole organismal phenotypic data are the largest obstacle to capitalising on phenomics for advancing our understanding of biological systems. We suggest that phenomics within the context of developing organismal form and function could provide an effective scaffold for addressing grand challenges in CDP and phenomics.

A phenomics approach reveals interspecific differences in integrated developmental responses to chronic elevated temperatures.

Phenomics, high-dimensional organismal phenotyping, is advanced as a solution to quantifying complex developmental responses to elevated temperatures. 'Energy proxy traits' (EPTs) measure the phenotype as a spectrum of energy values across different temporal frequencies from pixel value fluctuations of video. Although they have proven effective in measuring the biology of complex and dynamic developing organisms, their utility in assessing environmental sensitivity of different species is untested. Using EPTs, we assess the relative thermal sensitivities of embryos of three species of freshwater snail with marked differences in their developmental event timings. Embryos of Lymnaea stagnalis, Radix balthica and Physella acuta were videoed hourly for the duration of their embryonic development at two temperatures: 20°C and 25°C. The video was used to calculate EPTs for the duration of their embryonic development, and during discrete physiological windows in development. Changes in energy spectra during development identified marked differences in thermal sensitivities between species, and suggest a relatively heightened sensitivity of gross rates of embryonic physiology and behaviour in embryos of R. balthica, developmental-window-specific thermal responses that reflect ontogenetic differences in observable physiologies, and temperature-induced changes in physiological event timing. EPTs enabled comparison of high-dimensional spectral phenotypes, providing a unique capability for assessing sensitivity continuously in developing individuals. Such integrative and scalable phenotyping is a prerequisite for improved understanding of the sensitivity of early life stages of different species.

Phenomics enables measurement of complex responses of developing animals to global environmental drivers.

Phenomics offers technological advances for high-dimensional phenotyping, facilitating rapid, high-throughput assessment of physiological performance and has proven invaluable in global research challenges including drug discovery and food security. However, this rapidly growing discipline has remained largely inaccessible to the increasingly urgent challenge of assessing organismal functional sensitivity to global change drivers. Here, we investigate the response of an ecologically important marine invertebrate to multiple environmental drivers using Energy Proxy Traits (EPTs), a new approach for measuring complex phenotypes captured on video as a spectrum of energy levels across different temporal frequencies in fluctuating pixel values. We imaged three developmental stages of the common prawn Palaemon serratus at different salinities and temperatures, and measured EPTs and heart rate, a major proxy of physiological performance in ectotherms present across stages. Significant interactions were detected between temperature, developmental stage and salinity in frequency-specific energy levels. Despite cardiac activity being a significant contributor to the EPT spectra, treatment interactions were different from those observed on EPTs, highlighting additional phenotypic drivers of EPTs. Elevated temperature resulted in a shift of the EPT spectra towards higher frequency signals, indicating a reallocation of resources within the phenome. Using a non-linear dimensionality reduction, we interrogated the responses of EPT spectra in high-dimensional space. We discovered complex developmental-stage specific sensitivities, highlighting both the complexity of phenotypic responses, and the limits of using univariate approaches with pre-selected traits to assess responses to multiple global environmental drivers. EPTs are a high-dimensional, transferrable method of phenotyping, and are therefore highly relevant to addressing the current limitations of traditional methods of phenotyping applied to assessing biological sensitivity to drivers of global change. We predict that EPTs will become an important tool for indiscriminate phenotyping, transferrable between species, developmental stages and experimental designs.

Effect of Animal Stocking Density and Habitat Enrichment on Survival and Vitality of Wild Green Shore Crabs, Carcinus maenas, Maintained in the Laboratory.

The wide geographic distribution, large size and ease of capture has led to decapod crustaceans being used extensively in laboratory experiments. Recently in the United Kingdom decapod crustaceans were listed as sentient beings, resulting in their inclusion in animal care protocols. Ironically, little is known about how captive conditions affect the survival and general condition of wild decapod crustaceans. We used the green shore crab, Carcinus maenas, to investigate the effects of stocking density and shelter on survival and vitality indices during a 6 month period in the laboratory. Neither stocking density nor the presence of shelter affected survival. Stocking density also had no effect on the vitality indices (limb loss, claw strength, BRIX, righting time, leg flare and retraction). The presence of shelter did affect the number of limbs lost and the leg retraction response, but had no effect on the other vitality indices. All vitality indices changed, and mortality increased over time, independent of treatment: this became most apparent after 8 to 11 weeks storage in the laboratory. This decline in condition may have been due to repeated handling of the crabs, rather than the stocking conditions. In support of this, untracked, non-handled (control) individuals sustained a 4% mortality rate compared with 67% mortality in experimental crabs during the 6 month period. Although simple experimental monitoring of crabs with biweekly vitality tests only produced transient short-term stress events, the repeated handling over time apparently led to a cumulative stress and a deterioration in animal health. Bringing wild crustaceans into the laboratory and holding them, even with modest experimental manipulation, may result in high mortality rates. Researchers and animal care committees need to be aware that wild captive invertebrates will respond very differently to laboratory-bred vertebrates, and plan experiments accordingly.

HeartCV: a tool for transferrable, automated measurement of heart rate and heart rate variability in transparent animals.

Heart function is a key component of whole-organismal physiology. Bioimaging is commonly, but not exclusively, used for quantifying heart function in transparent individuals, including early developmental stages of aquatic animals, many of which are transparent. However, a central limitation of many imaging-related methods is the lack of transferability between species, life-history stages and experimental approaches. Furthermore, locating the heart in mobile individuals remains challenging. Here, we present HeartCV: an open-source Python package for automated measurement of heart rate and heart rate variability that integrates automated localization and is transferrable across a wide range of species. We demonstrate the efficacy of HeartCV by comparing its outputs with measurements made manually for a number of very different species with contrasting heart morphologies. Lastly, we demonstrate the applicability of the software to different experimental approaches and to different dataset types, such as those corresponding to longitudinal studies.

Identifying Frail Patients by Using Electronic Health Records in Primary Care: Current Status and Future Directions.

With the rapidly aging population, frailty, characterized by an increased risk of adverse outcomes, has become a major public health problem globally. Several frailty guidelines or consensuses recommend screening for frailty, especially in primary care settings. However, most of the frailty assessment tools are based on questionnaires or physical examinations, adding to the clinical workload, which is the major obstacle to converting frailty research into clinical practice. Medical data naturally generated by routine clinical work containing frailty indicators are stored in electronic health records (EHRs) (also called electronic health record (EHR) data), which provide resources and possibilities for frailty assessment. We reviewed several frailty assessment tools based on primary care EHRs and summarized the features and novel usage of these tools, as well as challenges and trends. Further research is needed to develop and validate frailty assessment tools based on EHRs in primary care in other parts of the world.

Consequences of thermal plasticity for hypoxic performance in coastal amphipods.

Physiological plasticity may confer an ability to deal with the effect of rapid climate change on aquatic ectotherms. However, plasticity induced by one stressor may only be adaptive in situ if it generates cross-tolerance to other stressors. Understanding the consequences of thermal acclimation on hypoxia thresholds is vital to understanding future climate-driven hypoxia. We tested if thermal acclimation benefits hypoxic performance in four closely-related amphipod species. The effects of thermal acclimation (7 days at 10 or 20 °C) on routine metabolic rate (RMR) and critical oxygen tensions (Pcrit) were determined at a standardised test temperature (20 °C). Gammarus chevreuxi and Echinogammarus marinus displayed increased Pcrit with acute warming but warm acclimation negated this increase. Pcrit of Gammarus duebeni was thermally insensitive. Gammarus zaddachi displayed increased Pcrit upon acute warming but little change via acclimation. Cross-tolerance between thermal plasticity and hypoxia may improve performance for some, but not all, species under future environmental change.