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The expensive-tissue hypothesis (ETH) posited a brain–gut trade-off to explain how humans evolved large, costly brains. Versions of the ETH interrogating gut or other body tissues have been tested in non-human animals, but not humans. We collected brain and body composition data in 70 South Asian women and used structural equation modelling with instrumental variables, an approach that handles threats to causal inference including measurement error, unmeasured confounding and reverse causality. We tested a negative, causal effect of the latent construct ‘nutritional investment in brain tissues’ (MRI-derived brain volumes) on the construct ‘nutritional investment in lean body tissues’ (organ volume and skeletal muscle). We also predicted a negative causal effect of the brain latent on fat mass. We found negative causal estimates for both brain and lean tissue (−0.41, 95% CI, −1.13, 0.23) and brain and fat (−0.56, 95% CI, −2.46, 2.28). These results, although inconclusive, are consistent with theory and prior evidence of the brain trading off with lean and fat tissues, and they are an important step in assessing empirical evidence for the ETH in humans. Analyses using larger datasets, genetic data and causal modelling are required to build on these findings and expand the evidence base.
Flow is a transcranial direct current stimulation (tDCS) treatment for depression without major side effects that patients use at home. Over 30 years of research/clinical use show tDCS is safe (Razza et al., 2020). Flow is CE-marked for treating depression in Europe. Recent NICE briefing published (NICE, 2023). The patient self-administers and remains awake (NICE, 2015), treatment sessions last for about 30 minutes, and are repeated 5 times weekly for three weeks (Flow, 2023). After the initial three-week period, patients self-administer 3 sessions per week for 3 weeks, and then as long as required (Flow, 2023). Meta-analyses of randomised sham-controlled trials (RCT) show tDCS is associated with significant improvements in depressive symptoms and high rates of clinical response and remission relative to placebo sham stimulation (Mutz et al., 2018, 2019; Moffa et al., 2020; Razza et al., 2020). Flow RCT study depression remission rates are 45% (Fu et al., In Press). Flow incorporates an evidence backed healthy lifestyle behaviour training software app, and depression symptom tracking that enables users to monitor their progress/symptoms. Training modules on: ‘Behaviour activation’, ‘Mindfulness’, ‘Exercise for your brain’, ‘An anti-depression diet’, and ‘Therapeutic sleep’. Flow also provides an integrated platform for clinicians to monitor use and depression symptoms.
In a first for the NHS, in a post-marketing informed consent study, NHFT's community mental health team (CMHT) offered Flow to their patients with a diagnosis of depression and evaluated the feasibility and impact.
Methods
Outcome measure data collection from baseline to 6 week follow-up point. Self-report measures used were depression: Personal Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS); health related quality of life: EQ-5D-5L; and functioning: Work and Social Adjustment Scale (WSAS). In-depth interviews were undertaken with 14 patients.
Results
There has been high level of adherence (70%) to treatment protocol. There has been statistically significant and ‘reliable improvement’ in depression symptoms. There was statistically significant improvements in real world meaningful functioning and quality of life. Most participants described a positive impact on depressive symptoms, sleep, and functioning.
Conclusion
Flow has been successfully integrated into CMHT treatment offer. It is important to offer CMHT patients an evidence-backed alternative to existing depression treatments (antiddepressant medication and talking therapies). Findings provide support for the approach of delivering together both tDCS and evidence-backed wellbeing behaviour therapy training to patients of CMHTs with experience of depression.
Among Líĺwat people of the Interior Plateau of British Columbia, an oral tradition relays how early ancestors used to ascend Qẃelqẃelústen, or Mount Meager. The account maintains that those climbers could see the ocean, which is not the case today, because the mountain is surrounded by many other high peaks, and the Strait of Georgia is several mountain ridges to the west. However, the mountain is an active and volatile volcano, which last erupted circa 2360 cal BP. It is also the site of the largest landslide in Canadian history, which occurred in 2010. Given that it had been a high, glacier-capped mountain throughout the Holocene, much like other volcanoes along the coastal range, we surmise that a climber may have reasonably been afforded a view of the ocean from its prior heights. We conducted viewshed analyses of the potential mountain height prior to its eruption and determined that one could indeed view the ocean if the mountain were at least 950 m higher than it is today. This aligns with the oral tradition, indicating that it may be over 2,400 years old, and plausibly in the range of 4,000 to 9,000 years old when the mountain may have been at such a height.
Magnetic reconnection is an important process in astrophysical environments, as it reconfigures magnetic field topology and converts magnetic energy into thermal and kinetic energy. In extreme astrophysical systems, such as black hole coronae and pulsar magnetospheres, radiative cooling modifies the energy partition by radiating away internal energy, which can lead to the radiative collapse of the reconnection layer. In this paper, we perform two- and three-dimensional simulations to model the MARZ (Magnetic Reconnection on Z) experiments, which are designed to access cooling rates in the laboratory necessary to investigate reconnection in a previously unexplored radiatively cooled regime. These simulations are performed in GORGON, an Eulerian two-temperature resistive magnetohydrodynamic code, which models the experimental geometry comprising two exploding wire arrays driven by 20 MA of current on the Z machine (Sandia National Laboratories). Radiative losses are implemented using non-local thermodynamic equilibrium tables computed using the atomic code Spk, and we probe the effects of radiation transport by implementing both a local radiation loss model and $P_{1/3}$ multi-group radiation transport. The load produces highly collisional, super-Alfvénic (Alfvén Mach number $M_A \approx 1.5$), supersonic (Sonic Mach number $M_S \approx 4-5$) strongly driven plasma flows which generate an elongated reconnection layer (Aspect Ratio $L/\delta \approx 100$, Lundquist number $S_L \approx 400$). The reconnection layer undergoes radiative collapse when the radiative losses exceed the rates of ohmic and compressional heating (cooling rate/hydrodynamic transit rate = $\tau _{\text {cool}}^{-1}/\tau _{H}^{-1}\approx 100$); this generates a cold strongly compressed current sheet, leading to an accelerated reconnection rate, consistent with theoretical predictions. Finally, the current sheet is also unstable to the plasmoid instability, but the magnetic islands are extinguished by strong radiative cooling before ejection from the layer.
This survey reflects on a creative workshop which the authors ran for the ‘The State of Urban History: Past, Present, Future’ conference (July 2023). ‘Making manifestos for urban history’ was an experiment to encourage small group work and co-operative outputs in a conference setting, allowing for an atypical ‘many-to-many’ model of participation. During the session, five groups each produced a manifesto poster addressing issues that they thought were important for the future of urban history. The survey sets out the form the workshop followed, considers those who were involved and comments on how successful the workshop was in fostering conference community and active learning. Feedback recorded at the end of the session indicated that it was indeed successful in both these areas. Overall, the workshop demonstrated that when urban historians work together across generations and continents, they produce work of real value, which is resilient and sustainable.
Three authigenic muscovite morphologies are associated with Norphlet Formation stylolitization observed in the Texaco Mobile Area Block 872 #1 well: l)large crystals of 1M muscovite, which grew in the stylolites with their c-axes parallel to the plane of maximum compressive stress; 2) fine-grained bundles of muscovite that occur as pore-fillings near stylolites; and 3) pods of fine-grained muscovite that exist within stylolite insoluble residue and that were precipitated as pore-filling muscovite before the host sandstone pressolved.
The population of large crystals of 1M muscovite grew at 51 ± 9 Ma, pore-filling muscovites precipitated at 77 ± 22 Ma, and muscovite pods have ages of 86 ± 16 Ma, as indicated by 40Ar/39Ar laser fusion. Apparent ages indicate that stylolitization was coincident with the beginning of organic maturation Zone 5 and could be the product of reservoir fluid pressure fluctuations induced by gas leakage. The lower Smackover Formation source/seal rock, acting as a pressure relief valve, could have been compromised by microfractures occurring during hydrocarbon generation and expulsion. Decreases in reservoir fluid pressure would have acted upon the sandstone framework by increasing the effective overburden pressure, thus making the rock more susceptible to pressure solution.
Stylolite frequency and quartz cement volume increase in the finer grained portion of the conventional core. Quartz cement volume correlates inversely to percent sandstone porosity. Apparent muscovite ages indicate that stylolitization occurred after hydrocarbon migration. Silica mobility was limited because pressure solution mineral products were precipitated from within grain films of irreducible water within the sandstone.
Stylolitization of quartz grains accounts for a minimum of 34% of the quartz cement in the upper cored section of the Norphlet Formation and minimum of 17% of the quartz cement in the lower cored Norphlet Formation. Quartz cement volumes are based on stylolite insoluble residue thickness and weight measurements of pyrobitumen within and nearby the insoluble residue seams. Stylolitization of K-feldspar and precipitation of muscovite can release additional silica which may have precipitated as quartz cement.
Edited by
Richard Williams, University of South Wales,Verity Kemp, Independent Health Emergency Planning Consultant,Keith Porter, University of Birmingham,Tim Healing, Worshipful Society of Apothecaries of London,John Drury, University of Sussex
The aim of this chapter is to provide a conceptual overview for emergency planners and responders of the different patterns of emergencies, incidents, disasters, and disease outbreaks (EIDD) and the challenges that they pose for mounting a mental health response. Issues covered include anticipating who is affected, where they are located, and how they can be identified and contacted, as well as other implications for public health and clinical services.
PD patients commonly exhibit executive dysfunction early in the disease course which may or may not predict further cognitive decline over time. Early emergence of visuospatial and memory impairments, in contrast, are more consistent predictors of an evolving dementia syndrome. Most prior studies using fMRI have focused on mechanisms of executive dysfunction and have demonstrated that PD patients exhibit hyperactivation that is dependent on the degree of cognitive impairment, suggestive of compensatory strategies. No study has evaluated whether PD patients with normal cognition (PD-NC) and PD patients with Mild Cognitive Impairment (PD-MCI) exhibit compensatory activation patterns during visuospatial task performance.
Participants and Methods:
10 PD-NC, 12 PD-MCI, and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task Force, Level II assessment (comprehensive assessment). Functional magnetic resonance imaging (fMRI) was performed during a motion discrimination task that required participants to identify the direction of horizontal global coherent motion embedded within dynamic visual noise under Low and High coherence conditions. Behavioral accuracy and functional activation were evaluated using 3 * 2 analyses of covariance (ANCOVAs) (group [HC, PD-NC, PD-MCI] * Coherence [High vs. Low]) accounting for age, sex, and education. Analyses were performed in R (v4.1.2(Team, 2013)).
Results:
PD-MCI (0.702± 0.269) patients exhibited significantly lower accuracy on the motion discrimination task than HC (0.853 ± 0.241; p = 0.033) and PD-NC (0.880 ± 0.208; p =0.039). A Group * Coherence interaction was identified in which several regions, including orbitofrontal, posterior parietal and occipital cortex, showed increased activation during High relative to Low coherence trials in the PD patient groups but not in the HC group. HC showed default mode deactivation and frontal-parietal activation during Low relative to High coherence trials that was not evident in the patient groups.
Conclusions:
PD-MCI patients exhibited worse visuospatial performance on a motion discrimination task than PD-NC and HC participants and exhibited hyperactivation of the posterior parietal and occipital regions during motion discrimination, suggesting possible compensatory activation.
In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al–Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community’s social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, ‘marrara’, at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71–1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
The IntCal family of radiocarbon (14C) calibration curves is based on research spanning more than three decades. The IntCal group have collated the 14C and calendar age data (mostly derived from primary publications with other types of data and meta-data) and, since 2010, made them available for other sorts of analysis through an open-access database. This has ensured transparency in terms of the data used in the construction of the ratified calibration curves. As the IntCal database expands, work is underway to facilitate best practice for new data submissions, make more of the associated metadata available in a structured form, and help those wishing to process the data with programming languages such as R, Python, and MATLAB. The data and metadata are complex because of the range of different types of archives. A restructured interface, based on the “IntChron” open-access data model, includes tools which allow the data to be plotted and compared without the need for export. The intention is to include complementary information which can be used alongside the main 14C series to provide new insights into the global carbon cycle, as well as facilitating access to the data for other research applications. Overall, this work aims to streamline the generation of new calibration curves.
Understanding parents’ communication preferences and how parental and child characteristics impact satisfaction with communication is vital to mitigate communication challenges in the cardiac ICU.
Methods
This cross-sectional survey was conducted from January 2019 to March 2020 in a paediatric cardiac ICU with parents of patients admitted for at least two weeks. Family satisfaction with communication with the medical team was measured using the Communication Assessment Tool for Team settings. Clinical characteristics were collected via Epic, Pediatric Cardiac Critical Care Consortium local entry and Society for Thoracic Surgeons Congenital Heart Surgery Databases. Associations between communication score and parental mood, stress, perceptions of clinical care, and demographic characteristics along with patient demographic and clinical characteristics were examined. Multivariable ordinal models were conducted with characteristics significant in bivariate analysis.
Results
In total, 93 parents of 84 patients (86% of approached) completed surveys. Parents were 63% female and 70% White. Seventy per cent of patients were <6 months old at admission, 25% had an extracardiac abnormality, and 80% had a cardiac surgery this admission. Parents of children with higher pre-surgical risk of mortality scores (OR 2.875; 95%CI 1.076–7.678), presence of surgical complications (72 [63.0, 75.0] vs. 64 [95%CI 54.6, 73] (p = 0.0247)), and greater satisfaction with care in the ICU (r = 0.93922; p < 0.0001) had significantly higher communication scores.
Conclusion
These findings can prepare providers for scenarios with higher risk for communication challenges and demonstrate the need for further investigation into interventions that reduce parental anxiety and improve communication for patients with unexpected clinical trajectories
Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.
Methods:
This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.
Key Results:
A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.
Conclusions:
The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
OBJECTIVES/GOALS: The purpose of this small survey-based study was to characterize the current role of neurocritical care physicians in traumatic brain injury (TBI) systems of care and research. In doing so, we aim to highlight potential roles of neurology providers in the medical management and enhancement of translational science in the field of TBI. METHODS/STUDY POPULATION: Between April and June 2021, a web-based survey was disseminated by email to members of the Neurocritical Care Society. The survey was open to all physician providers. A total of 36 surveys were completed. The survey consisted of 18 questions with pre-defined answer choices. Survey questions aimed to determine areas of practice, primary clinical specialty, hospital practice setting, provider involvement in TBI care, provider involvement in TBI research, and current research roles. RESULTS/ANTICIPATED RESULTS: 92% of survey respondents were in the United States (n=33), representing all national regions. 75% of the physicians were neurocritical care trained (n=27). 69% of providers were practicing in academic institutions while 78% were at sites designated as Level I trauma centers. All respondents managed acute TBI, but 50% served as consultants rather than being the primary service provider. At their sites of practice, 31% of patients were on non-neuroscience services, especially those with non-neurologic traumatic injury. Only 36% reported that TBI protocols were written and adhered to at their site. Only 44% reported that TBI research was performed at their site, while 50% had interest in participating in TBI research. TBI was the primary area of research for 17% of physicians. DISCUSSION/SIGNIFICANCE: This small physician survey highlights heterogeneity in TBI systems-based practice and research roles. Areas of potential improvement include greater involvement of neurocritical care physicians in TBI management, protocol-building and implementation, and TBI research. Reasons for current barriers are multifactorial and will be discussed.
Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012–2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46–59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.
Tree-ring series offer considerable potential for the development of environment-sensitive proxy records. However, with traditional increment cores, only small amounts of wood are often available from annual tree-ring sequences. For this reason, it is important to understand the reliability (and reproducibility) of radiocarbon measurements obtained from small-sized samples. Here we report the F14C results from the Chronos 14Carbon-Cycle Facility of modern tropical Australian tree samples over a range of four graphite target sizes from the same rings. Our study shows that similar precision can be obtained from full-sized, half-sized, as well as small-sized graphite targets using standard pretreatment and analysis procedures. However, with a decline in sample size, there was an increase seen in the associated variance of the ages and the smallest target weights started showing a systematic bias. Wiggle-matching accuracy tests, comparing the Southern Hemisphere post-bomb atmospheric calibration curve to the different sample weight sequences, were all significant except for the 200 μgC graphite targets. Our results indicate that samples smaller than 350 μgC have limited accuracy and precision. Overall, reliable measurements of F14C sequences from tree-ring records across a range of sample sizes, with best results found using graphitized samples >350 μgC.
While quantum accelerometers sense with extremely low drift and low bias, their practical sensing capabilities face at least two limitations compared with classical accelerometers: a lower sample rate due to cold atom interrogation time; and a reduced dynamic range due to signal phase wrapping. In this paper, we propose a maximum likelihood probabilistic data fusion method, under which the actual phase of the quantum accelerometer can be unwrapped by fusing it with the output of a classical accelerometer on the platform. Consequently, the recovered measurement from the quantum accelerometer is used to estimate bias and drift of the classical accelerometer which is then removed from the system output. We demonstrate the enhanced error performance achieved by the proposed fusion method using a simulated 1D accelerometer precision test scenario. We conclude with a discussion on fusion error and potential solutions.
This book argues that the traditional government approach of exhorting individuals to live healthier lifestyles is not enough - action to promote public health needs to take place not just through public agencies, but also by engaging community assets and resources in their broadest sense.
Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43–8.03), social care (aOR 2.63, 1.22–5.67) or healthcare (aOR 2.31, 1.29–4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03–4.62), visit a pub (aOR 2.87, 1.11–7.37) and smoke or vape (aOR 1.54, 1.02–2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.
Sleep is vital for health and wellbeing across the lifecourse. Ethnic differences have been observed with regards to the prevalence and predictors of self-reported sleep problems. An understanding of sleep experiences with ageing and across ethnicities is required to better support older people. Open-ended interviews were conducted with 23 people living in Aotearoa/New Zealand aged 61–92 years (12 Māori and 11 non-Māori) concerning current sleep status, changes over their lifecourse and personal strategies for supporting good sleep. Participants typically expressed satisfaction with current sleep (usually pertaining to duration) or feelings that sleep was compromised (usually pertaining to waking function). Comparisons to a socially perceived ‘ideal’ sleep were common, with sleep transitions presented as a gradual and accepted part of ageing. Participants resisted medicalising sleep disruptions in older age. While participants were aware of ways to enhance their sleep, many acknowledged engaging in practices that undermined it. Unique insights from some Māori participants indicated that sleep disruptions were not so readily pathologised compared to Western views and that sleeplessness could provide opportunity for cultural or spiritual connection. Common narratives underpinning the themes were: ‘You don't need as much sleep when you're older’, ‘Sleep just fits in’ and ‘Having the time of my life’. Findings provide personal experiences and cultural interpretations relating to sleep and ageing. This provides the foundation for future participatory research to co-design sleep health messages which are meaningful for ageing well across ethnicities.