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Abstract We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.

Infant electrocardiograms (ECGs) and heart rates (HRs) are very useful biosignals for psychological research and clinical work, but can be hard to analyse properly, particularly longform (≥5 min) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open source ECG approaches are tested on infant datasets. The best-performing open source method is then modified to maximise its performance on infant data (e.g., including a 15 Hz high-pass filter, adding local peak correction). The HR signal is then subsequently analysed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HRs. A Signal Quality Index (SQI) for HR is also developed, providing insights into where a signal is recoverable and where it is not, allowing for more confidence in the analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for the future analysis of infant ECGs and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world, large datasets.

Abstract Background Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. Method The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. Results In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world’s first real-time patient treatment verification system (Watchdog); (vi) inventing the effective ‘EAT’ psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. Conclusion Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

We present a complicated case of mixed mechanism glaucoma in the setting of failed corneal transplant and aphakia. The patient was a 54-year old male with HLA B27 uveitis and prior open globe injury. He was left aphakic after cataract extraction and had a subsequent corneal transplant for bullous keratopathy. Due to elevated intraocular pressure in the setting of a failed corneal graft, the decision was made to insert a pars plana tube shunt and perform repeat penetrating keratoplasty as a combined case with the glaucoma, cornea, and retina services. We illustrate the surgical steps and decision making and in this complex case.

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Abstract Infant mortality remains high and uneven in much of sub-Saharan Africa. Even low-cost, highly effective therapies can only save lives in proportion to how successfully they can be targeted to those children who, absent the treatment, would have died. This places great value on maximizing the accuracy of any targeting or means-testing algorithm. Yet, the interventions that countries deploy in hopes of reducing mortality are often targeted based on simple models of wealth or income or a few additional variables. Examining 22 countries in sub-Saharan Africa, we illustrate the use of flexible (machine learning) risk models employing up to 25 generally available pre-birth variables from the Demographic and Health Surveys. Using these models, we construct risk scores such that the 10 percent of the population at highest risk account for 15-30 percent of infant mortality, depending on the country. Successful targeting in these models turned on several variables other than wealth, while models that employ only wealth data perform little or no better than chance. Consequently, employing such data and models to predict high-risk births in the countries studied flexibly could substantially improve the targeting and thus the life-saving potential of existing interventions.

Physical literacy (PL), a concept commonly associated with the early years, physical education, and youth sport development, can become a meaningful determinant of health and longevity for the adult and older adult population. A review of 55 recent publications from 2018 to 2023 that encompassed physical literacy conceptual frameworks, assessments, and intervention-based studies was undertaken through an heuristic inspired by the philosophy which gave birth to PL. With particular interest in how PL has evolved in response to the needs of an aging population, this position paper tracks a key shift in focus from the individual to the relational context. It references positive interaction and social participation in recent models as significant features of an across-the-lifespan PL perspective.The concluding position is that fostering joyful inter-action be at the heart of PL promotion, resource development and assessment practices, especially in the case of an aging population.

Abstract Studies of neurodegenerative disease risk in gout are contradictory. Relationships with neuroimaging markers of brain structure, which may offer insights, are uncertain. Here we investigated associations between gout, brain structure, and neurodegenerative disease incidence. Gout patients had smaller global and regional brain volumes and markers of higher brain iron, using both observational and genetic approaches. Participants with gout also had higher incidence of all-cause dementia, Parkinson’s disease, and probable essential tremor. Risks were strongly time dependent, whereby associations with incident dementia were highest in the first 3 years after gout diagnosis. These findings suggest gout is causally related to several measures of brain structure. Lower brain reserve amongst gout patients may explain their higher vulnerability to multiple neurodegenerative diseases. Motor and cognitive impairments may affect gout patients, particularly in early years after diagnosis.

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals (“Member Advocates”) who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.

Background: Esthetic anterior composite restorations are very challenging. They constitute a main part of the clinical practice of restoring teeth with resin composites. Distinctive variations in composite material selection and technique of application in anterior teeth exist when compared to the practice of restoring posterior teeth with resin composites. In a continuation of a previous assessment of class II resin composite practice, a cross-sectional survey study was performed to determine the awareness of general dental practitioners in Saudi Arabia about resin composite restorations in anterior teeth and to provide evidence-based recommendations to improve their practice. Methods: A total of 500 dental practitioners from different provinces in Saudi Arabia were invited to participate in an online questionnaire which comprised four domains and included a total of sixteen questions addressing aspects regarding the selection of resin composites, cavity configuration, etching protocol, light-curing technique, liner application, application of poly-chromatic composite, as well as finishing and polishing procedures. Chi square testing and descriptive statistics were used to analyze the attained data. Results: From 250 respondents, the greatest participation was from the Eastern and Middle provinces of Saudi Arabia. Female dentists participated less than males. There was no general agreement between participants regarding the resin composite material or the employed technique of application in restoring anterior tooth defects. Respondents indicated that discoloration and hypersensitivity were the most common reasons for patient’s dissatisfaction with resin composites in anterior teeth. Conclusions: Dental practitioners are highly encouraged to improve their clinical practice of restoring anterior teeth using resin composites with the focus upon continuous education programs, online webinars, and workshops.

ObjectiveBlack individuals living with psychosis are at risk for stigma and marginalization due to systematic discrimination and barriers to receiving treatment. Social contact-based interventions have the potential to reduce stigma; however, interventions with elements specific to the experiences of Black youth are limited. Therefore, we aimed to gather input from Black youth living with psychosis to develop a social contact-based, brief video intervention to reduce public stigma toward Black youth with psychosis.MethodsTwo 90-min focus groups were conducted with seven young Black individuals ages 18–30 with First Episode Psychosis from OnTrackNY. Participants were asked about their experiences of stigma and racial discrimination, and their perspectives on a video intervention. Focus group transcripts were analyzed using thematic content analysis.ResultsThemes that emerged included: the salience of stigma and racial experiences for some participants and not others; the linking of religiosity and symptoms in Black communities; the importance of taking responsibility for recovery as a coping strategy to counteract stigma; and mixed views on creating a video intervention specific to Black youth.ConclusionMeaningful and empowering involvement of individuals with lived experience of psychosis is essential to create stigma reducing interventions. Input from Black youth living with psychosis assisted in developing a culturally tailored brief video-based intervention to reduce public stigma toward Black youth with psychosis that included information about the protagonist’s experience of race and mental illness, specifically family, religious, and community-based experiences.

Falls have always been one of the major threats to the health and well-being of elderly people, particularly for those living alone. Both wearable and non-wearable fall detection systems have already been developed. However, the fall detection systems using WiFi channel state information (CSI) have attracted a significant interest from researchers due to their non-intrusive and low-cost nature. There are existing machine learning (ML) based fall detection systems using WiFi CSI; however, most systems trained with comprehensive datasets tend to achieve relatively lower accuracy compared to that of the systems trained with less inclusive datasets. To address these issues, we propose a novel, deep learning based fall detection technique. First, we implement different WiFi CSI collection tools and evaluate their potential for fall detection. To develop a highly accurate fall detection technique, we construct a comprehensive dataset, which consists of over 700 CSI samples including different types of falls and other daily activities, performed in four different indoor environments on and off the dominant paths. With this dataset, we then develop a deep learning based classifier using an image classification algorithm. The proposed technique, unlike the other fall detection systems, only requires down sampling and reshaping in pre-processing. The proposed fall detection system is evaluated with the constructed dataset, and it outperforms two other existing systems. It achieves over 96% accuracy for CSI collected in all four environments and 99% accuracy for CSI collected in certain combinations of the environments.

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

Genomic selection has recently become an established part of breeding strategies in cereals. However, a limitation of linear genomic prediction models for complex traits such as yield is that these are unable to accommodate Genotype by Environment effects, which are commonly observed over trials on multiple locations. In this study, we investigated how this environmental variation can be captured by the collection of a large number of phenomic markers using high-throughput field phenotyping and whether it can increase GS prediction accuracy. For this purpose, 44 winter wheat (Triticum aestivum L.) elite populations, comprising 2,994 lines, were grown on two sites over 2 years, to approximate the size of trials in a practical breeding programme. At various growth stages, remote sensing data from multi- and hyperspectral cameras, as well as traditional ground-based visual crop assessment scores, were collected with approximately 100 different data variables collected per plot. The predictive power for grain yield was tested for the various data types, with or without genome-wide marker data sets. Models using phenomic traits alone had a greater predictive value (R2 = 0.39–0.47) than genomic data (approximately R2 = 0.1). The average improvement in predictive power by combining trait and marker data was 6%–12% over the best phenomic-only model, and performed best when data from one full location was used to predict the yield on an entire second location. The results suggest that genetic gain in breeding programmes can be increased by utilisation of large numbers of phenotypic variables using remote sensing in field trials, although at what stage of the breeding cycle phenomic selection could be most profitably applied remains to be answered.

Introduction Surgery is the most common treatment for colorectal cancer (CRC) and can cause relative long average length of stay (LOS) and high risks of unplanned readmissions and complications. Enhanced Recovery After Surgery (ERAS) pathways can reduce the LOS and postsurgical complications. Digital health interventions provide a flexible and low-cost way of supporting patients to achieve this. This protocol describes a trial aiming to evaluate the effectiveness and cost-effectiveness of the RecoverEsupport digital health intervention in decreasing the hospital LOS in patients undergoing CRC surgery.Methods and analysis The two-arm randomised controlled trial will assess the effectiveness and cost-effectiveness of the RecoverEsupport digital health intervention compared with usual care (control) in patients with CRC. The intervention consists of a website and a series of automatic prompts and alerts to support patients to adhere to the patient-led ERAS recommendations. The primary trial outcome is the length of hospital stay. Secondary outcomes include days alive and out of hospital; emergency department presentations; quality of life; patient knowledge and behaviours related to the ERAS recommendations; health service utilisation; and intervention acceptability and use.Ethics and dissemination The trial has been approved by the Hunter New England Research Ethics Committee (2019/ETH00869) and the University of Newcastle Ethics Committee (H-2015-0364). Trial findings will be disseminated via peer-reviewed publications and conference presentations. If the intervention is effective, the research team will facilitate its adoption within the Local Health District for widespread adaptation and implementation.Trial registration number ACTRN12621001533886.

Abstract Twitter has been responsible for some major stock market news in the recent past, from rogue CEOs damaging their company to very active world leaders asking for brand boycotts, but despite its impact Twitter has still not been as impactful on markets as traditional news sources. In this paper we examine whether daily news sentiment of several companies and Twitter sentiment from their CEOs have an impact on their market performance and whether traditional news sources and Twitter activity of heads of government impact the benchmark indexes of major world economies over a period spanning the outbreak of the SAR-COV-2 pandemic. Our results indicate that there is very limited correlation between Twitter sentiment and price movements and that this does not change much when returns are taken relative to the market or when the market is calm or turbulent. There is almost no correlation under any circumstances between non-financial news sources and price movements, however there is some correlation between financial news sentiment and stock price movements. We also find this correlation gets stronger when returns are taken relative to the market. There are fewer companies correlated in both turbulent and calm economic times. There is no clear pattern to the direction and strength of the correlation, with some being strongly negatively correlated and others being strongly positively correlated, but in general the size of the correlation tends to indicate that price movement is driving sentiment, except in the turbulent economic times of the SARS-COV-2 pandemic in 2020.

Beekeeping in Ireland has been strongly impacted by the parasitic mite Varroa destructor, whose introduction caused alarming honeybee colony losses. If unmitigated, these losses could lead to the disappearance of the native honeybee subspecies, Apis mellifera mellifera, with severe consequences for local biodiversity. Although beekeepers play a pivotal role in mitigating this crisis, beekeeping in Ireland is less intensive compared to other European regions, lacking significant infrastructure or support. These circumstances offer a unique opportunity for the development of national programmes that promote sustainable beekeeping practices for varroa control. Notably, local accounts highlight an increasing number of beekeepers successfully managing colonies in the absence of treatments, indicating a potential avenue for developing varroa-resistant stocks through selection of local colonies. Through a survey, we explored beekeeper’s opinions and attitudes towards future national projects focused on the development of sustainable beekeeping practices and selection for varroa resistance. The findings confirm the hobbyist nature of Irish beekeepers and their preference for the native honey bee. Some beekeepers were reported to be effectively controlling varroa without treatment, yielding comparable survivals to those using treatments. The majority expressed preference towards a varroa-resistant line if it were of native origin; a few were open to importing non-Irish lines. Overall, a strong willingness to participate in a national breeding programme was expressed. These findings highlight a prime opportunity for Ireland to establish a community-driven strategy based on sustainable beekeeping practices for safeguarding native honeybees and local biodiversity.

There have been sustained efforts toward using naturalistic methods in developmental science to measure infant behaviors in the real world from an egocentric perspective because statistical regularities in the environment can shape and be shaped by the developing infant. However, there is no user-friendly and unobtrusive technology to densely and reliably sample life in the wild. To address this gap, we present the design, implementation and validation of the EgoActive platform, which addresses limitations of existing wearable technologies for developmental research. EgoActive records the active infants’ egocentric perspective of the world via a miniature wireless head-mounted camera concurrently with their physiological responses to this input via a lightweight, wireless ECG/acceleration sensor. We also provide software tools to facilitate data analyses. Our validation studies showed that the cameras and body sensors performed well. Families also reported that the platform was comfortable, easy to use and operate, and did not interfere with daily activities. The synchronized multimodal data from the EgoActive platform can help tease apart complex processes that are important for child development to further our understanding of areas ranging from executive function to emotion processing and social learning.

Objective: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. Design: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. Participants: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. Methods: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. Main Outcome Measures: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. Results: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5 × 10−5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. Conclusions: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.

Modelling and predicting individual differences in task-fMRI activity can have a wide range of applications from basic to clinical neuroscience. It has been shown that models based on resting-state activity can have high predictive accuracy. Here we propose several improvements to such models. Using a sparse ensemble learner, we show that (i) features extracted using Stochastic Probabilistic Functional Modes (sPROFUMO) outperform the previously proposed dual-regression approach, (ii) that the shape and overall intensity of individualised task activations can be modelled separately and explicitly, (iii) training the model on predicting residual differences in brain activity further boosts individualised predictions. These results hold for both surface-based analyses of the Human Connectome Project data as well as volumetric analyses of UK-biobank data. Overall, our model achieves state of the art prediction accuracy on par with the test-retest reliability of task-fMRI scans, suggesting that it has potential to supplement traditional task localisers.

Handwriting communication is a long-established human activity that has survived into the 21st century. Accordingly, research interest in handwritten documents, both historical and modern, is significant. The way we write has changed significantly over the past few centuries. For example, texts of the Middle Ages were often written and copied by anonymous scribes. The writing of each scribe, known as his/her "scribal hand" is unique. It can be differentiated using a variety of consciously and unconsciously produced features. Distinguishing between these different scribal hands is a central focus of the humanities research field known as "paleography." Character recognition within each scribal hand has also posed an interesting challenge. Some issues make these digital processes difficult, such as paper degradation and the soiling of the manuscript page. Thus, in this paper, we propose an investigation in both perspectives, character recognition and writer identification, in medieval manuscripts to better understand the specific behaviour of two 800-year-old scribes based on their manuscripts in comparison with a modern calligrapher. The experiments demonstrated that degradation and tremor can influence the analysis of medieval handwriting documents. However, the results presented an efficient accuracy with a better accuracy rate in letter classification than in writer identification.La communication manuscrite est une longue tradition humaine qui a persisté jusqu’à nos jours, au 21e siècle. Par conséquent, l’intérêt de la recherche concernant des documents manuscrits historiques et modernes est grand. La façon dont nous écrivons a changé au cours des derniers siècles. Par exemple, des textes du Moyen Âge ont souvent été écrits et copiés par des scribes. L’écriture de chaque scribe, appelée son « écriture scribale » (anglais scribal hand), est unique. Nous pouvons la différencier en observant une gamme de caractéristiques produites consciemment et inconsciemment. Faire la distinction entre ces écritures scribales différentes est au centre des préoccupations du domaine de recherche de paléographie. La reconnaissance de caractères dans chacune des écritures scribales pose des défis intéressants. Certains problèmes, tels que la dégradation de papier et l’encrassement de la page manuscrite, rendent difficiles ces processus numériques. Dans cet article, nous proposons ainsi une enquête sur les deux perspectives, la reconnaissance de caractères et l’identification de scribes, dans les manuscrits médiévaux dans le but de mieux comprendre le comportement spécifique de deux scribes vivant il y a 800 ans, en se basant sur leurs manuscrits en comparaison avec un calligraphe moderne. Les expériences démontrent que la dégradation et le tremblement peuvent influer sur l’analyse des documents manuscrits médiévaux. Cependant, les résultats ont présenté une précision efficace, avec un meilleur taux de précision dans la reconnaissance de caractères que dans celui de l’identification de scribe.

Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

Promoting mental health addresses a global societal challenge. Nature connectedness, or relatedness to natural systems, is associated with increased well-being and mental health. Among urban populations, nature connectedness has been reported as lower. Nature connectedness in urban settings has been somewhat overlooked by researchers. This cross-sectional online study addressed this issue by identifying socio-demographic predictors of urban nature connectedness among 165 students, aged 20 to 40, from the Technical University of Munich. Analysis of the data from 153 female university students was conducted using ordinal regressions, (a) separately and (b) merged with their 12 male counterparts. A separate gender analysis for males could not be performed, due to sample size limitations. Although access to nature and a considerable nature dose in terms of frequency and duration of nature contact were noted, possibly achieved through the engagement in outdoor activities, urban nature connectedness was rather low. Results showed that urban nature connectedness was negatively predicted by living in a rural area and positively predicted by engagement in outdoor activities and increased hours per week spent in nature. This information can help researchers operationalize the construct of urban nature connectedness. Furthermore, it can aid the development of interventions aimed at promoting urban nature connectedness, by encouraging urban inhabitants to (repeatedly) get in contact with and spend time in provided high-quality urban nature (e.g., during outdoor activities). To draw conclusions about causality, further research is required to identify a clear cause-effect relationship between socio-demographic characteristics and urban nature connectedness. Based on a researched dose-response relationship, a(n) (inter)national recommendation for the duration of nature contact should be established to promote urban nature connectedness and, therewith, health in urban inhabitants. Future research should also investigate further potential individual influencing factors, as well as gender and within/between-country differences among urban inhabitants.

Background Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection. Methods We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20–02/21/21 and in round 2 from 12/18/20–02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity. Results In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician’s Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68]. Conclusions SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting—particularly working in the ICU—is associated with higher risk for SARS-CoV-2 infection.

Background Panton-Valentine Leukocidin (PVL) toxin in Staphylococcus aureus has been associated with both severe pneumonia and skin and soft tissue infections. However, there are only limited data on how this virulence factor may influence the clinical course or complications of bacteremic S. aureus infections. Methods Between September 2016 and March 2018, S. aureus isolates from clinical cultures from hospitals in an academic medical center underwent comprehensive genomic sequencing. Four hundred sixty-nine (29%) of 1681 S. aureus sequenced isolates were identified as containing the genes that encode for PVL. Case patients with one or more positive blood cultures for PVL were randomly matched with control patients having positive blood cultures with lukF/lukS-PV negative (PVL strains from a retrospective chart review). Results 51 case and 56 control patients were analyzed. Case patients were more likely to have a history of injection drug use, while controls more likely to undergo hemodialysis. Isolates from 78.4% of case patients were methicillin resistant as compared to 28.6% from control patients. Case patients had a higher incidence of pneumonia and skin and soft tissue infection and longer duration of fever without differences in length of bacteremia. Clinical cure or expiration was comparable. Conclusions These results are consistent with prior observations associating the PVL toxin with both community-acquired MRSA strains as well as severe staphylococcal pneumonia. The presence of the PVL toxin does not appear to otherwise influence the natural history of bacteremic S. aureus disease other than in prolonging the duration of fever.

A wind-shear now-casting system for Hong Kong International Airport is described. The system has been configured and run retrospectively for the period from January to April 2018 at 20-min intervals using two sets of meteorological inputs to quantify uncertainty. Outputs from the system include calculations of headwind for the northerly and southerly runways at the airport. Six metrics have been defined that attempt to identify areas of strong wind shear; these involve quantification of headwind and headwind gradient in both the horizontal and vertical directions. Receiver operating characteristic (ROC) curves have been generated for all metrics, runways, and meteorological conditions using pilot wind-shear reports to define wind-shear events. These curves allow for derivation of metric thresholds that could be used within an operational system to provide wind-shear alerts. The skill of the system for the 4-month period was quantified in terms of the probability of detection (POD, ideal value 1.0) of wind-shear events; system performance was better for the southerly runway, with the majority of POD values in the range 0.6 to 0.8.

BackgroundObsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts, urges, or images (obsessions) and repetitive physical or mental behaviors (compulsions). Previous factor analytic and clustering studies suggest the presence of three or four subtypes of OCD symptoms. However, these studies have relied on predefined symptom checklists, which are limited in breadth and may be biased toward researchers’ previous conceptualizations of OCD. ObjectiveIn this study, we examine a large data set of freely reported obsession symptoms obtained from an OCD mobile app as an alternative to uncovering potential OCD subtypes. From this, we examine data-driven clusters of obsessions based on their latent semantic relationships in the English language using word embeddings. MethodsWe extracted free-text entry words describing obsessions in a large sample of users of a mobile app, NOCD. Semantic vector space modeling was applied using the Global Vectors for Word Representation algorithm. A domain-specific extension, Mittens, was also applied to enhance the corpus with OCD-specific words. The resulting representations provided linear substructures of the word vector in a 100-dimensional space. We applied principal component analysis to the 100-dimensional vector representation of the most frequent words, followed by k-means clustering to obtain clusters of related words. ResultsWe obtained 7001 unique words representing obsessions from 25,369 individuals. Heuristics for determining the optimal number of clusters pointed to a three-cluster solution for grouping subtypes of OCD. The first had themes relating to relationship and just-right; the second had themes relating to doubt and checking; and the third had themes relating to contamination, somatic, physical harm, and sexual harm. All three clusters showed close semantic relationships with each other in the central area of convergence, with themes relating to harm. An equal-sized split-sample analysis across individuals and a split-sample analysis over time both showed overall stable cluster solutions. Words in the third cluster were the most frequently occurring words, followed by words in the first cluster. ConclusionsThe clustering of naturally acquired obsessional words resulted in three major groupings of semantic themes, which partially overlapped with predefined checklists from previous studies. Furthermore, the closeness of the overall embedded relationships across clusters and their central convergence on harm suggests that, at least at the level of self-reported obsessional thoughts, most obsessions have close semantic relationships. Harm to self or others may be an underlying organizing theme across many obsessions. Notably, relationship-themed words, not previously included in factor-analytic studies, clustered with just-right words. These novel insights have potential implications for understanding how an apparent multitude of obsessional symptoms are connected by underlying themes. This observation could aid exposure-based treatment approaches and could be used as a conceptual framework for future research.

A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e., possession of protective HLA alleles or the absence of critical cell surface receptors). In this study, we examine a cohort of HIV-1 infected individuals with a documented history of sustained low viral loads in the absence of therapy. Through in vitro analyses of cells from these individuals, we have determined that infected individuals with naturally low viral loads are capable of controlling spreading infection in vitro in a CD8+ T-cell dependent manner. This control is lost when viral load is suppressed by antiretroviral therapy and correlates with a clinical CD4:CD8 ratio of

Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, ‘ground truth’ validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how “functional connectivity” from fMRI and “tractographic connectivity” from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.

Germ-cell-tumours (GCTs) are heterogeneous and management is complex. The current conventional biomarkers, alpha-fetoprotein and human-chorionic-gonadotropin (HCG), have limited utility for diagnosis/follow-up as secretion is restricted to specific malignant-GCT subtypes and long half-life can make interpretation and clinical decision-making challenging. We sought to identify circulating microRNAs that reflected choriocarcinoma disease activity more accurately than HCG in a metastatic primary mediastinal nonseminomatous-GCT (PMNSGCT) case with elevated diagnostic serum HCG (>250,000 U/L), consistent with pure choriocarcinoma. We undertook comprehensive microRNA profiling (n = 754 microRNAs) using two 384-well TaqMan Low-Density-Array cards in 16 serum samples; 10 from PMNSGCT diagnosis/follow-up and six controls. Key findings underwent confirmatory qRT-PCR. We identified a serum panel of choriocarcinoma-specific ‘chromosome-19-microRNA-cluster’ (C19MC) microRNAs that were highly elevated at diagnosis but fell rapidly on treatment and normalised before the second full chemotherapy course. We also re-confirmed serum elevation of the previously identified malignant-GCT marker miR-371a-3p at diagnosis. These circulating microRNA markers reflected choriocarcinoma disease activity more accurately than serum HCG and real-time knowledge would have assisted clinical decision-making. With further study, these microRNA markers will facilitate future management of such patients and are likely to result in improved outcomes.

Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain.

Methods for now-casting adverse weather conditions with the potential to cause disruption to aircraft landings often make use of real-time measurements at high temporal resolution. This paper describes processing methodologies developed to derive meteorological parameters from such measurements recorded in the vicinity of Hong Kong International Airport, specifically a radiometer in King’s Park, a wind profiler and surface anemometer on Cheung Chau Island and weather buoys in the Pearl River estuary. These parameters are suitable for use as input to a now-casting application of the computationally efficient airflow model, FLOWSTAR, which has previously been shown to predict mountain waves generated by flow over Lantau Island to the southeast of the airport. Radiosonde data from King’s Park have been used to test the radiometer processing method; the novel approach of using minimum and maximum potential temperature deviations from a series of height-dependent linear profiles to derive radiometer inversion layer parameters generates data that compares well with values derived from corresponding radiosonde profiles. Mountain wave strength depends on the magnitude of wind speed in the inversion layer; wind profiler data can be used to estimate typical and maximum wind speeds and associated wind directions using estimates of inversion layer depth derived from the radiometer data. With estimates of surface sensible heat flux appropriate for the airport’s coastal location calculated using a marine boundary layer scheme, a dataset of meteorological parameters at 20-min resolution has been derived for input into the FLOWSTAR model. The combination of automated meteorological data processing methods and flow field modelling has the potential to form part of a now-casting system for determining strong wind shear conditions at the airport.

Ambient air pollution from PM2.5 is a major risk to human and environmental health, with significant impacts on mortality and morbidity. Mitigation policies—which may be regional or national in extent—need to consider both primary and secondary particles to be effective, balancing within-region emissions and longer-range transport phenomena. The modelling system WRF-CMAQ was used to simulate the impact of emissions reductions in the West Midlands region of the UK, evaluating the change in total PM2.5 and in its primary and secondary components. Domestic combustion, road transport and agriculture emissions were reduced individually or in combination, at a national or at local level. Combined reduction of road transport and agriculture emissions showed the strongest reduction (29%) in average PM2.5 if applied at national level. At the local level, reductions from domestic combustion were shown to be the most effective policy (13.4% on average). Secondary inorganic fractions of PM2.5 are the most abundant, with 25% NO3− 21% SO42− and 13% NH4+ on average. Scenario analysis shows that the contribution of secondary components to the fractional change of PM2.5 dominates for national policies (up to 0.86 for NO3−) when road transport and agriculture activities are reduced, while at the regional level the elemental and organic carbon fractional changes are dominant (up to 0.64 for organic carbon).

Abstract Background There is an urgent need for developing objective, effective and convenient measurements to help clinicians accurately identify bradykinesia. The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping (FT) that uses evolutionary algorithms (EAs) and explore whether it can be used to identify early stage Parkinson’s disease (PD). Methods One hundred and seven PD, 41 essential tremor (ET) patients and 49 normal controls (NC) were recruited. Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger. Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs. The output from the device (referred to as "PD-Monitor") scaled from − 1 to + 1 (where higher scores indicate greater severity of bradykinesia). Meanwhile, the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) FT item. Results With an increasing MDS-UPDRS FT score, the PD-Monitor score from the same hand side increased correspondingly. PD-Monitor score correlated well with MDS-UPDRS FT score (right side: r = 0.819, P = 0.000; left side: r = 0.783, P = 0.000). Moreover, PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup (FT bradykinesia scored from 1 to 3) were all higher than that in NC. Receiver operating characteristic (ROC) curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy (≥89.7%) in the right dominant hand. Furthermore, PD-Monitor scores could discriminate early stage PD from NC, with area under the ROC curve greater than or equal to 0.899. Additionally, ET without bradykinesia could be differentiated from PD by PD-Monitor scores. A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides. Conclusions Our study demonstrated that a simple to use device employing classifiers derived from EAs could not only be used to accurately measure different severity of bradykinesia in PD, but also had the potential to differentiate early stage PD from normality.

This paper is based on the eco-pedagogical aspiration to live with domesticated animals in accordance with Alphonso Lingis's Community of those who have nothing in common. I draw upon this remarkable text as well as Lingis's animal writings in describing moments and movements of pathic community. Such a community in affective affiliation with one another, where symbiotic relations are possible and bodily kinships are exercised, exemplifies what is possible in more rational human communities where domesticating impulses seek to harness the vital powers of coconstitutive life. Of telling significance are predatory threats, the manner in which they appear, and the protectionist responses they occasion. By recasting these threats and responses in terms of motional affordances, it may well be possible to move with non-human creatures, both literally and figuratively, beyond the anthropocentric confines of domestication. Animals with whom we appear to have nothing specifically, or in species terms, in common can show us how to cultivate more pathic communities of our own kind.

Notch can drive senescence in a cell contact dependent manner. Here the authors show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously via the JAG1-NOTCH-HMGA1 interplay during senescence.

While gene expression noise in single-celled organisms is well understood, it is less so in the context of tissues. Here the authors show that coupling between cells in tissues can increase or decrease cell-to-cell variability depending on the level of noise intrinsic to the regulatory networks.

Patients with Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) show between-group comorbidity and symptom overlap, and within-group heterogeneity. Resting state functional connectivity might provide an alternate, biologically informed means by which to stratify patients with GAD or MDD. Resting state functional magnetic resonance imaging data were acquired from 23 adults with GAD, 21 adults with MDD, and 27 healthy adult control participants. We investigated whether within- or between-network connectivity indices from five resting state networks predicted scores on continuous measures of depression and anxiety. Successful predictors were used to stratify participants into two new groups. We examined whether this stratification predicted attentional bias towards threat and whether this varied between patients and controls. Depression scores were linked to elevated connectivity within a limbic network including the amygdala, hippocampus, VMPFC and subgenual ACC. Patients with GAD or MDD with high limbic connectivity showed poorer performance on an attention-to-threat task than patients with low limbic connectivity. No parallel effect was observed for control participants, resulting in an interaction of clinical status by resting state group. Our findings provide initial evidence for the external validity of stratification of MDD and GAD patients by functional connectivity markers. This stratification cuts across diagnostic boundaries and might valuably inform future intervention studies. Our findings also highlight that biomarkers of interest can have different cognitive correlates in individuals with versus without clinically significant symptomatology. This might reflect protective influences leading to resilience in some individuals but not others. Keywords: Resting state, Connectivity, Generalized anxiety disorder, Major depressive disorder, Biomarker, Limbic, Amygdala, Attention, Stratification

Evidence of pain perception in fish is well established, but analgesic use in aquaculture is limited. The objective was to investigate the comparative pharmacokinetics of flunixin administered intramuscularly (IM) and meloxicam administered IM or orally (PO) in tilapia. Two hundred and seventy fish were assigned to 1 of 3 treatment groups: flunixin meglumine IM (2.2 mg/kg); meloxicam IM (1 mg/kg); or meloxicam PO (1 mg/kg). Blood and tissue samples were collected from 6 fish per treatment at 14 time points for 10 days. Drug concentrations were determined using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Plasma concentration versus time data were analyzed with a non-compartmental approach using a commercially available software. Flunixin reached a mean maximum concentration (Cmax) of 4826.7 ng/mL at 0.5 h, had a terminal half-life (T1/2) of 7.34 h, and an area under the concentration–time curve extrapolated to infinity (AUCINF_obs) of 25,261.62 h·ng/mL. Meloxicam IM had a T1/2 of 9.4 h after reaching a Cmax of 11.3 ng/mL at 2 h, with an AUCINF_obs of 150.31 h·ng/mL. Meloxicam PO had a T1/2 of 1.9 h after reaching a Cmax of 72.2 ng/mL at 2 h, with an AUCINF_obs of 400.83 h·ng/mL. Tissue concentrations of both drugs were undetectable by 9 h. Flunixin reached a sufficient plasma concentration to potentially have an analgesic effect, while meloxicam, when administered at the given dosage, likely would not.

The “life phenomenology” theme of the 35th International Human Science Research Conference challenged participants to consider pressing questions of life and of living with others of our own and other-than-human kinds. The theme was addressed by keynote speakers Maxine Sheets-Johnstone, Ralph Acampora and David Abram who invoked a motile, affective and linguistic awareness of how we might dwell actively and ethically amongst human communities and with the many life forms we encounter in the wider, wilder world we have in common. Conference participants were provoked to consider the following questions: “How might phenomenology have us recognize a primacy of movement and bring us in touch with the motions and gestures of the multiple lifeworlds of daily living? What worlds from ecology to technology privilege certain animations? What are the affects and effects of an enhanced phenomenological sensitivity? What senses, feelings, emotions and moods of self-affirmation and responsiveness to others sustain us in our daily lives? And to what extent might the descriptive, invocative, provocative language of phenomenology infuse the human sciences and engender a language for speaking directly of life?”

While interactions with other animate beings seem mostly to serve our own human interests, there are, at times, fugitive glimpses, passing contacts, momentary motions, and fleeting feelings of vital connection with other life forms. Life phenomenology attempts to realize these relational, interactive and intercorporeal possibilities. It challenges the language game of presuming the muteness and bruteness of non-human creatures and, at best, of speaking for them. It critiques the capture of non-human species within the inhibiting ring of human functions and forms to reveal feelings and flows of interspecies commonality. It brings to expression the experiences of being moved to act and speak with others who do not share the human tongue. In part a critique of the logocentric, anthropocentric phenomenologies of intentionality, life phenomenology is more positively a means of coming to terms with the life-affirming kinetic, kinesthetic and affective dynamics of interspecies relationality. I take up the interrogation of this phenomenality, this humanimality, with the assistance of phenomenological scholarship that lends fuller credence to the experiences we have of moving in concert with other animate beings. In doing so, I aim to show the important insights that life phenomenology offers us in fostering not only greater appreciation of, responsivenss to and connection with other animals, but also in indicating the qualitative dynamics of relating with greater animate consciousness to one anotherof our own animal kind.

The control of parasitic sea lamprey in Lake Champlain has been a necessary component of its fishery restoration and recovery goals for 30 years. While adopting the approach of the larger and established sea lamprey control program of the Laurentian Great Lakes, local differences emerged that shifted management focus and effort as the program evolved. Increased investment in lamprey assessment and monitoring revealed under-estimations of population density and distribution in the basin, where insufficient control efforts went unnoticed. As control efforts improved in response to a better understanding of the population, the effects of lamprey on the fishery lessened. A long-term evaluation of fishery responses when lamprey control was started, interrupted, delayed, and enhanced provided evidence of a recurring relationship between the level of control effort applied and the measured suppression of the parasitic sea lamprey population. Changes in levels of control efforts over time showed repeatedly that measurable suppression of the parasitic population required effective control of 80% of the known larval population. Understanding the importance of assessment and monitoring and the relationship between control effort and population suppression has led to recognition that a comprehensive, not incremental, approach is needed to achieve effective control of sea lamprey in Lake Champlain.

[This corrects the article DOI: 10.1371/journal.pbio.1000521.].

This paper investigates and analyses the features of a non-mainstream pedagogy, educational context and learning environment by presenting a counter-model which contrasts with the currently dominant educational project, an emergent global educational movement known as the Slow Education Movement. It demonstrates how the associated principles and praxes of a particular ethos and its philosophical foundations guide teaching and learning. Set against the background of the Slow Education Movement, the paper draws on a case study to illustrate some of the foundational principles and practices of that movement. The paper outlines the educational ethos, philosophy, processes and practices of Blue Gum Community School and how the teaching and learning practices contribute to the development of skills that increase student resilience, positive emotion, engagement and meaning in a learning environment of authentic student research and academic rigor. The paper fulfils an introductory and exploratory purpose into the area of non-mainstream education which, it is envisaged, will be built upon through further research and deeper analysis of the methods and strategies employed in the teaching and learning processes employed in such educational environments.

El artículo ofrece un análisis del modo en que la historiografía reciente ha contribuido a nuestra comprensión sobre la Revolución Rusa, identificando las tendencias y problemas analíticos que han ocupado a los historiadores desde, aproximadamente, los inicios del siglo XXI. Comienza con un bosquejo de ciertas tendencias interpretativas que han tenido influencia en la historiografía reciente y luego rastrea algunos de los temas que han atraído el mayor interés académico.

Background: Bowel cancer screening reduces cancer-specific mortality. There is a socioeconomic gradient in the uptake of the English NHS Bowel Cancer Screening Programme (BCSP), which may lead to inequalities in cancer outcomes. Objective: To reduce socioeconomic inequalities in uptake of the NHS BCSP’s guaiac faecal occult blood test (gFOBt) without compromising uptake in any socioeconomic group. Design: Workstream 1 explored psychosocial determinants of non-uptake of gFOBt in focus groups and interviews. Workstream 2 developed and tested four theoretically based interventions: (1) ‘gist’ information, (2) a ‘narrative’ leaflet, (3) ‘general practice endorsement’ (GPE) and (4) an ‘enhanced reminder’ (ER). Workstream 3 comprised four national cluster randomised controlled trials (RCTs) of the cost-effectiveness of each intervention. Methods: Interventions were co-designed with user panels, user tested using interviews and focus groups, and piloted with postal questionnaires. RCTs compared ‘usual care’ (existing NHS BCSP invitations) with usual care plus each intervention. The four trials tested: (1) ‘gist’ leaflet (n = 163,525), (2) ‘narrative’ leaflet (n = 150,417), (3) GPE on the invitation letter (n = 265,434) and (4) ER (n = 168,480). Randomisation was based on day of mailing of the screening invitation. The Index of Multiple Deprivation (IMD) score associated with each individual’s home address was used as the marker of socioeconomic circumstances (SECs). Change in the socioeconomic gradient in uptake (interaction between treatment group and IMD quintile) was the primary outcome. Screening uptake was defined as the return of a gFOBt kit within 18 weeks of the invitation that led to a ‘definitive’ test result of either ‘normal’ (i.e. no further investigation required) or ‘abnormal’ (i.e. requiring referral for further testing). Difference in overall uptake was the secondary outcome. Results: The gist and narrative trials showed no effect on the SECs gradient or overall uptake (57.6% and 56.7%, respectively, compared with 57.3% and 58.5%, respectively, for usual care; all p-values > 0.05). GPE showed no effect on the gradient (p = 0.5) but increased overall uptake [58.2% vs. 57.5% in usual care, odds ratio (OR) = 1.07, 95% confidence interval (CI) 1.04 to 1.10; p

Attention is drawn to the movements of the body and to the ethical imperative that emerges in compelling, flowing moments of teaching. Such moments of teaching are not primarily intellectual, discursive events, but physical, sensual experiences in which the body surrenders to its own movements. Teaching is recognized momentarily as a carnal intensity embedded in and emerging from the flesh. The ethical imperative to this teaching is felt proprioceptively and kinaesthetically when one holds in self-motion the well-being of another as being of the same flesh. The teaching caress offers a primary example. This gesture of intimacy discloses an embodied ethic that contrasts with the transcendental ethics of curricular prescriptions, professional codes of conduct, and the presumptions of self-monitoring behavior. It is a gesture of care for another person, without fastidious carefulness. It is a gesture of pure duration, without sanctimonious purity, in its contact with the beauty, truth and value of the teachable moment. From earliest engagements with children to the dynamics of the university classroom, what makes for good teaching is essentially attentiveness to intimate gestures, such as the caress, that guide teachers kinethically in the moment.

Abstract We analyzed land‐cover and forest vegetation data from nearly 25,000 permanent plots distributed across 50 national parks in the eastern United States, along with the matrix around each park, to examine structural characteristics of park forests in relation to their surrounding landscape. Over 2000 of these plots are part of the National Park Service (NPS) Inventory and Monitoring Program (I&M), and the remaining 22,500+ plots are part of the US Forest Service (USFS) Forest Inventory and Analysis (FIA) Program. This is the first study to compare forest structure in protected lands with the surrounding forest matrix over such a large area of the United States and is only possible because of the 10+ years of data that are now publicly available from USFS‐FIA and NPS I&M. Results of this study indicate that park forests, where logging is largely prohibited, preserve areas of regionally significant older forest habitat. Park forests consistently had greater proportions of late‐successional forest, greater live tree basal area, greater densities of live and dead large trees, and considerably larger volume of coarse woody debris. Park forests also had lower tree growth and mortality rates than matrix forests, suggesting different forest dynamics between park and matrix forests. The divergent patterns we observed between matrix and park forests were similar to those reported in studies that compared managed and old‐growth forests, although the differences in our study were less pronounced. With the majority of park forests in second growth, eastern parks may be a more realistic baseline to compare with the more intensively managed matrix forests. We recommend that park managers allow natural disturbance and the development of older structure to continue in park forests. In addition, long‐term maintenance of regional biodiversity will likely require increases in older forest structure in the matrix. As the NPS moves into its next century of land preservation, we encourage managers to consider parks important components of a larger regional effort to preserve biodiversity and ecosystem processes in eastern US forests. The data collected by NPS I&M programs will continue to provide important information and guidance toward these regional conservation efforts.