The impact of water on slip system activity in olivine and the formation of bimodal crystallographic preferred orientations

Crystallographic preferred orientations (CPOs) in olivine are widely used to infer the mechanisms, conditions, and kinematics of deformation of mantle rocks. Recent experiments on water-saturated olivine were the first to produce a complex CPO characterised by bimodal orientation distributions of both [100] and [001] axes and inferred to form by combined activity of (001)[100], (100)[001], and (010)[100] slip. This result potentially provides a new microstructural indicator of deformation in the presence of elevated concentrations of intracrystalline hydrous point defects and has implications for the interpretation of seismic anisotropy. Here, we document a previously unexplained natural example of this CPO type in a xenolith from Lesotho and demonstrate that it too may be explained by elevated concentrations of hydrous point defects. We test and confirm the hypothesis that combined (001)[100], (100)[001], and (010)[100] slip were responsible for formation of this CPO by (1) using high-angular resolution electron backscatter diffraction to precisely characterise the dislocation types present in both the experimental and natural samples and (2) employing visco-plastic self-consistent simulations of CPO evolution to assess the ability of these slip systems to generate the observed CPO. Finally, we utilise calculations based on effective-medium theory to predict the anisotropy of seismic wave velocities arising from the CPO of the xenolith. Maxima in S-wave velocities and anisotropy are parallel to both the shear direction and shear plane normal, whereas maxima in P-wave velocities are oblique to both, adding complexity to interpretation of deformation kinematics from seismic anisotropy.D. Wallis, L.N. Hansen, and A.J. Wilkinson acknowledge support from the Natural Environment Research Council Grant NE/M000966/1. M. Tasaka acknowledges support through a JSPS Research Fellowship for Young Scientists (26-4879) and the Japan Society for the Promotion of Science (16K17832). D.L. Kohlstedt acknowledges support through NASA Grant NNX15AL53G. K.M. Kumamoto acknowledges support through NSF Division of Earth Science grants 1255620 and 1625032

Altered landing mechanics are shown by male youth soccer players at different stages of maturation

Objectives Examine the effects of maturation on single leg jumping performance in elite male youth soccer players. Design Cross sectional. Setting Academy soccer clubs. Participants 347 male youth players classified as either pre, circa or post-peak height velocity (PHV). Main outcome measures Single leg countermovement jump (SLCMJ) height, peak vertical landing forces (pVGRF), knee valgus and trunk side flexion. Results Vertical jump height and absolute pVGRF increased with each stage of maturation (p < 0.001; d = 0.85–2.35). Relative to body weight, significantly higher landing forces were recorded on the left leg in circa versus post-PHV players (p < 0.05; d = −0.40). Knee valgus reduced with maturation but the only notable between-group differences were shown in post-PHV players (p < 0.05; d = 0.67); however, greater ipsilateral lateral trunk flexion angles was also present and these differences were significantly increased relative to circa-PHV players (p < 0.05; d = 0.85). Conclusion Periods of rapid growth are associated with landing kinetics which may heighten injury risk. While reductions in knee valgus were displayed with maturation; a compensatory strategy of greater trunk lateral flexion was evident in post-PHV players and this may increase the risk of injury

Rederivation of transgenic mice from iPS cells derived from frozen tissue

In mice, induced pluripotent stem (iPS) cells with embryonic stem (ES)-like characteristics have been derived by ectopic expression of four transcription factors in somatic cells: Sox2, Oct3/4, Klf4 and/or c-Myc. To date, iPS cells have only be made from freshly harvested tissues and cells. However, if iPS cells could be derived from frozen tissues and cells, then cryopreservation of tissues such as mouse tails could conceivably become a reliable alternative to the more traditional formats, like germplasm and ES cells, for the archiving of genetically altered mouse lines. To test this hypothesis, we sought to demonstrate that a live transgenic mouse line could be recovered from transgenic iPS cells derived from cryopreserved mouse tissues. Tails and tail-derived fibroblasts from a DsRED transgenic mouse were cryopreserved in the presence of 5% dimethylsulfoxide (DMSO) in liquid nitrogen for 1 week and 1 month, respectively. Afterward, tissues and cells were thawed and underwent nuclear reprogramming by molecular transfection to derive iPS cells which generated germline confirmed transgenic mice. Our results demonstrate for the first time that iPS cells can be efficiently derived from frozen-stored-thawed tail tissue and fibroblasts and used to re-establish a transgenic mouse line. Therefore, this study provides conclusive evidence that, as a practical matter, frozen tails and fibroblasts can be used as an effective and reliable alternative to frozen germplasm and ES cells for the storage, maintenance, and distribution of genetically-altered mutant mice

Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection

Background Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery. Methods Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale. Results Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with &gt;1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature, but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors. Conclusions SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.</p

A qualitative study of professional and client perspectives on information flows and decision aid use

<p>Abstract</p> <p>Background</p> <p>This paper explores the meanings given by a diverse range of stakeholders to a decision aid aimed at helping carers of people in early to moderate stages of dementia (PWD) to select community based respite services. Decision aids aim to empower clients to share decision making with health professionals. However, the match between health professionals' perspectives on decision support needs and their clients' perspective is an important and often unstudied aspect of decision aid use.</p> <p>Methods</p> <p>A secondary analysis was undertaken of qualitative data collected as part of a larger study. The data included twelve interviews with carers of people with dementia, three interviews with expert advisors, and three focus groups with health professionals. A theoretical analysis was conducted, drawing on theories of 'positioning' and professional identity.</p> <p>Results</p> <p>Health professionals are seen to hold varying attitudes and beliefs about carers' decision support needs, and these appeared to be grounded in the professional identity of each group. These attitudes and beliefs shaped their attitudes towards decision aids, the information they believed should be offered to dementia carers, and the timing of its offering. Some groups understood carers as needing to be protected from realistic information and consequently saw a need to filter information to carer clients.</p> <p>Conclusion</p> <p>Health professionals' beliefs may cause them to restrict information flows, which can limit carers' ability to make decisions, and limit health services' ability to improve partnering and shared decision making. In an era where information is freely available to those with the resources to access it, we question whether health professionals should filter information.</p

Radial structure, inflow and central mass of stationary radiative galaxy clusters

We analyse the radial structure of self-gravitating spheres consisting of multiple interpenetrating fluids, such as the X-ray emitting gas and the dark halo of a galaxy cluster. In these dipolytropic models, the adiabatic dark matter sits in equilibrium, while the gas develops a gradual, smooth, quasi-stationary cooling flow. Both affect and respond to the collective gravitational field. We find that all subsonic, radially continuous, steady solutions require a non-zero minimum central point mass. For Mpc-sized haloes with 7–10 effective degrees of freedom (F2), the minimum central mass is compatible with observations of supermassive black holes. Smaller gas mass influxes enable smaller central masses for wider ranges of F2. The halo comprises a sharp spike around the central mass, embedded within a core of nearly constant density (at 101–102.5 kpc scales), with outskirts that attenuate and naturally truncate at finite radius (several Mpc). The gas density resembles a broken power law in radius, but the temperature dips and peaks within the dark core. A finite minimum temperature occurs due to gravitational self-warming, without cold mass dropout nor needing regulatory heating. X-ray emission from the intracluster medium mimics a β-model plus bright compact nucleus. Near-sonic points in the gas flow are bottlenecks to the allowed steady solutions; the outermost are at kpc scales. These sites may preferentially develop cold mass dropout during strong perturbations off equilibrium. Within the sonic point, the profile of gas specific entropy is flatter than s∝r1/2, but this is a shallow ramp and not an isentropic core. When F2 is large, the inner halo spike is only marginally Jeans stable in the central parsec, suggesting that a large non-linear disturbance could trigger local dark collapse on to the central object

The effect of different cardiovascular risk presentation formats on intentions, understanding and emotional affect: a randomised controlled trial using a web-based risk formatter (protocol)

Background The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect. Methods/design A randomised controlled trial comprising four arms, with a between subjects design will be performed. There will be two intervention groups and two control groups. The first control comprises a pre-intervention questionnaire and presents risk in a bar graph format. The second control presents risk in a bar graph format without pre-intervention questionnaire. These two control groups are to account for the potential Hawthorne effect of thinking about cardiovascular risk before viewing actual risk. The two intervention groups comprise presenting risk in either a pictogram or metonym format (image depicting seriousness of having a myocardial infarction). 800 individuals' aged between 45 and 64 years, who have not been previously diagnosed with heart disease and have access to a computer with internet, will be given a link to a website comprising a risk calculator and electronic questionnaires. 10-year risk of having a coronary heart disease event will be assessed and presented in one of the three formats. A post-intervention questionnaire will be completed after viewing the risk format. Main outcome measures are (i) intention to change behaviour, (ii) understanding of risk information, (iii) emotional affect and (iv) worry about future heart disease. Secondary outcomes are the sub-components of the theory of planned behaviour: attitudes, perceived behavioural control and subjective norms. Discussion Having reviewed the literature, we are not aware of any other studies which have used the assessment of actual risk, in a trial to compare different graphical cardiovascular risk presentation formats. This trial will provide data about which graphical cardiovascular risk presentation format is most effective in encouraging behaviour change to reduce cardiovascular risk. Trial registration Current Controlled Trials ISRCTN9131931

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability

Including ELSI research questions in newborn screening pilot studies

Background The evidence review processes for adding new conditions to state newborn screening (NBS) panels rely on data from pilot studies aimed at assessing the potential benefits and harms of screening. However, the consideration of ethical, legal, and social implications (ELSI) of screening within this research has been limited. This paper outlines important ELSI issues related to newborn screening policy and practices as a resource to help researchers integrate ELSI into NBS pilot studies. Approach Members of the Bioethics and Legal Workgroup for the Newborn Screening Translational Research Network facilitated a series of professional and public discussions aimed at engaging NBS stakeholders to identify important existing and emerging ELSI challenges accompanying NBS. Results Integrating ELSI questions into pilot studies will help NBS programs to better understand the potential impact of screening for a new condition on newborns and families, and make crucial policy decisions aimed at maximized benefits and mitigating the potential negative medical or social implications of screening

The Yin and Yang of Yeast Transcription: Elements of a Global Feedback System between Metabolism and Chromatin

When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions