JURNAL AGROTEKNOLOGI
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Novel cognitive markers for early diagnosis and monitoring of progressive supranuclear palsy
No full textComputing p-adic L-functions of totally real fields
No full textWe describe an algorithm for computing -adic L-functions of characters of totally real fields, using the Fourier expansions of diagonal restrictions of Hilbert modular forms
The many faces of health justice
No full textThis paper develops the idea of health justice as a plural conception. It draws on the literature on justice from philosophy and economics, and investigates its application and reach in the space of health. Several distinctions are invoked in identifying and contrasting different facets of health justice and injustice. These include active versus passive injustice; process fairness versus substantive justice; comparative versus non comparative justice; compensatory and distributive justice. Within distributive justice, the health implications of alternate principles – viz. equality, priority, sufficiency, and efficiency – are examined and evaluated. Many faces of health justice are thus exposed which help to address the varieties of injustice observed in the health sphere
Developing a framework for public involvement in mathematical and economic modelling: bringing new dynamism to vaccination policy recommendations
No full textObjectives: The Mathematical and Economic Modelling for Vaccination and Immunisation Evaluation (MEMVIE) programme aimed to explore, capture and support the potential contribution of the public to mathematical and economic modelling, in order to identify the values that underpin public involvement (PI) in modelling and co-produce a framework that identifies the nature and type of PI in modelling and supports its implementation.
Methods: We established a PI Reference Group, who worked collaboratively with the academic contributors to create a deliberative knowledge space, which valued different forms of knowledge, expertise and evidence. Together, we explored the key steps of mathematical and economic methods in 21 meetings during 2015–2020. These deliberations generated rich discussion, through which we identified potential points of public contribution and the values that underpin PI in modelling. We iteratively developed a framework to guide future practice of PI in modelling.
Results: We present the MEMVIE Public Involvement Framework in two forms: a short form to summarise key elements, and a long form framework to provide a detailed description of each potential type of public contribution at each stage of the modelling process. At a macro level, the public can contribute to reviewing context, reviewing relevance, assessing data and justifying model choice, troubleshooting, and interpreting and reviewing outcomes and decision making. The underpinning values that drive involvement include the public contributing to the validity of the model, potentially enhancing its relevance, utility and transparency through diverse inputs, and enhancing the credibility, consistency and continuous development through scrutiny, in addition to contextualising the model within a wider societal view.
Discussion and Conclusion: PI in modelling is in its infancy. The MEMVIE Framework is the first attempt to identify potential points of collaborative public contribution to modelling, but it requires further evaluation and refinement that we are undertaking in a subsequent study
Design and rationale of the EMPA-VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
No full textAims
Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium-glucose co-transporter-2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR-Reduced trial and cardiovascular mortality in the EMPA-REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR).
Methods and results
The EMPA-VISION trial is a double-blind, randomized, placebo-controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine-to-adenosine triphosphate ratio, as measured by 31Phosphorus-MRS.
Conclusions
EMPA-VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR-Reduced and EMPEROR-Preserved)
Is a procedural learning deficit a causal risk factor for developmental language disorder or dyslexia? a meta-analytic review
No full textImpaired procedural learning has been suggested as a possible cause of developmental dyslexia (DD) and Developmental Language Disorder (DLD). We evaluate this theory by performing a series of meta-analyses on evidence from the six procedural learning tasks that have most commonly been used to test this theory: the serial reaction time, Hebb learning, artificial grammar and statistical learning, weather prediction and contextual cueing tasks. Studies using serial reaction time and Hebb learning tasks yielded small group deficits in comparisons between language impaired and typically developing controls (g = -0.30 and -0.32 respectively). However, a meta-analysis of correlational studies showed that the serial reaction time task was not a reliable correlate of language-related ability in unselected samples (r = 0.03). Larger group deficits were, however, found in studies using artificial grammar and statistical learning tasks (g = -0.48) and the weather prediction task (g = -0.63). Possible reasons for the discrepancy in results from different tasks that all purportedly measure procedural learning are highlighted. We conclude that current data do not provide an adequate test of the theory that a generalized procedural learning deficit is a causal risk factor for developmental dyslexia or developmental language disorder
Framing energetic top-quark pair production at the LHC
No full textTop-quark pair production is central to many facets of LHC physics. At leading order, the top and anti-top are produced in a back-to-back topology, however this topology accounts only for a minority of the events with TeV-scale momentum transfer that contain a tt¯ pair. The remaining events instead involve the splitting of an initial or final-state gluon to tt¯. We provide simple quantitative arguments that explain why this is the case, and examine the interplay between different topologies and a range of variables that characterise the event hardness. We then develop a method to classify the topologies of individual events and use it to illustrate our findings in the context of simulated events, using both top partons and suitably defined fiducial tops. For events with large tt¯ invariant mass, we comment on additional features that have important experimental and theoretical implications
Secondary prevention of dementia: combining risk factors and scalable screening technology
No full textAlzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia. Over a third of dementia cases are estimated to be due to potentially modifiable risk factors, thus offering opportunities for both identification of those most likely to be in early disease as well as secondary prevention. Diabetes, hypertension and chronic kidney failure have all been linked to increased risk for AD and dementia and through their high prevalence are particularly apt targets for initiatives to reduce burden of AD. This can take place through targeted interventions of cardiovascular risk factors (shown to improve cognitive outcomes) or novel disease modifying treatments in people with confirmed AD pathology. The success of this approach to secondary prevention depends on the availability of inexpensive and scalable methods for detecting preclinical and prodromal dementia states. Developments in blood-based biomarkers for Alzheimer's disease are rapidly becoming a viable such method for monitoring large at-risk groups. In addition, digital technologies for remote monitoring of cognitive and behavioral changes can add clinically relevant data to further improve personalisation of prevention strategies. This review sets the scene for this approach to secondary care of dementia through a review of the evidence for cardiovascular risk factors (diabetes, hypertension and chronic kidney disease) as major risk factors for AD. We then summarize the developments in blood-based and cognitive biomarkers that allow the detection of pathological states at the earliest possible stage. We propose that at-risk cohorts should be created based on the interaction between cardiovascular and constitutional risk factors. These cohorts can then be monitored effectively using a combination of blood-based biomarkers and digital technologies. We argue that this strategy allows for both risk factor reduction-based prevention programmes as well as for optimisation of any benefits offered by current and future disease modifying treatment through rapid identification of individuals most likely to benefit from them
Clinical and demographic correlates of accelerometer-measured physical activity in participants enrolled in the OPTIMISE HFpEF study
No full textAims: This study aimed to measure physical activity (PA) in participants with suspected Heart failure with preserved ejection fraction (HFpEF) and assess associations between PA and participant characteristics.
Methods: Adults with presumed HFpEF were recruited and received diagnostic evaluation and clinical assessment. PA was objectively measured using accelerometers over seven days. To examine predictors of PA, best subset analysis was used, with the optimal model defined as that with the lowest Bayesian information criterion (BIC).
Results: 124 participants with presumed HFpEF who had valid accelerometer data were included in this study. 76 were confirmed by a cardiologist as meeting the European Society of Cardiology diagnosis criteria for HFpEF. The median age of all participants was 80.1 years, and 47.4% were female. Patients spent most of each 24-hour period at low-intensity PA and few or no durations at high-intensity PA, with lower activity for those with HFpEF. Gait speed was the best univariate correlate of activity levels (adjusted R2 0.29). The optimal model using best subsets regression included six variables, and improved adjusted R2 to 0.47. In the model, lower levels of PA were associated with slower gait speed, lower levels of anxiety, higher levels of depression, past smoking history, a confirmed HFpEF diagnosis and higher BMI.
Conclusion: Participants demonstrated very low PA levels. The study has identified important patient characteristics associated with PA, which may help to identify those most in need of interventions. Notably, participants with confirmed HFpEF were more inactive than participants with other heart failure phenotypes
Angular precision of radical pair compass magnetoreceptors
No full textThe light-dependent magnetic compass sense of night-migratory songbirds is thought to rely on magnetically sensitive chemical reactions of radical pairs in cryptochrome proteins located in the birds’ eyes. Recently, an information theory approach was developed that provides a strict lower bound on the precision with which a bird could estimate its head direction using only geomagnetic cues and a cryptochrome-based radical pair sensor. By means of this lower bound, we show here how the performance of the compass sense could be optimized by adjusting the orientation of cryptochrome molecules within photoreceptor cells, the distribution of cells around the retina, and the effects of the geomagnetic field on the photochemistry of the radical pair