Foundational Aspects for Incorporating Dependencies in Copula-Based Bayesian Networks Using Structured Expert Judgments, Exemplified by the Ice Sheet-Sea Level Rise Elicitation.

The work presented here marks a further advance in expert uncertainty quantification. In a recent probabilistic evaluation of ice sheet process contributions to sea level rise, tail dependence was elicited and propagated through an uncertainty analysis for the first time. The elicited correlations and tail dependencies concerned pairings of three processes: Accumulation, Discharge and Run-off, which operate on major ice sheets in the West and East Antarctic and in Greenland.

JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.

Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h.

Ice Sheet and Climate Processes Driving the Uncertainty in Projections of Future Sea Level Rise: Findings From a Structured Expert Judgement Approach.

The ice sheets covering Antarctica and Greenland present the greatest uncertainty in, and largest potential contribution to, future sea level rise. The uncertainty arises from a paucity of suitable observations covering the full range of ice sheet behaviors, incomplete understanding of the influences of diverse processes, and limitations in defining key boundary conditions for the numerical models. To investigate the impact of these uncertainties on ice sheet projections we undertook a structured expert judgement study.

A retrospective assessment of COVID-19 model performance in the USA.

Coronavirus disease 2019 (COVID-19) forecasts from over 100 models are readily available. However, little published information exists regarding the performance of their uncertainty estimates (i.e.

Comprehensive evidence implies a higher social cost of CO.

The social cost of carbon dioxide (SC-CO) measures the monetized value of the damages to society caused by an incremental metric tonne of CO emissions and is a key metric informing climate policy. Used by governments and other decision-makers in benefit-cost analysis for over a decade, SC-CO estimates draw on climate science, economics, demography and other disciplines. However, a 2017 report by the US National Academies of Sciences, Engineering, and Medicine (NASEM) highlighted that current SC-CO estimates no longer reflect the latest research.

Mortality Attributable to Long-Term Exposure to Ambient Fine Particulate Matter: Insights from the Epidemiologic Evidence for Understudied Locations.

Epidemiologic cohort studies have consistently demonstrated that long-term exposure to ambient fine particles (PM) is associated with mortality. Nevertheless, extrapolating results to understudied locations may involve considerable uncertainty. To explore this issue, this review discusses the evidence for (i) the associated risk of mortality, (ii) the shape of the concentration-response function, (iii) a causal interpretation, and (iv) how the source mix/composition of PM and population characteristics may alter the effect.

Carpal tunnel syndrome and Raynaud's phenomenon: a narrative review.

Background: Raynaud's phenomenon (RP) is a recognized symptom associated with carpal tunnel syndrome (CTS) and is also the vascular manifestation of hand arm vibration syndrome (HAVS). The symptoms of HAVS and CTS are such that there is a significant possibility of misdiagnosis and an incorrect attribution of vascular and sensory symptoms. An understanding of the relationship between RP and CTS is essential when undertaking health surveillance of vibration-exposed workers presenting with combined vascular and sensory symptoms.

Vine Regression with Bayes Nets: A Critical Comparison with Traditional Approaches Based on a Case Study on the Effects of Breastfeeding on IQ.

Regular vines (R-vines) copulas build high dimensional joint densities from arbitrary one-dimensional margins and (conditional) bivariate copula densities. Vine densities enable the computation of all conditional distributions, though the calculations can be numerically intensive. Saturated continuous nonparametric Bayes nets (CNPBN) are regular vines.

The role of the super-relaxed state of myosin in human metabolism.

Background: The super-relaxed state of myosin (SRX) plays a fundamental role in maintaining the low resting metabolic rate of skeletal muscle. Our previous work on this state has been in animal models. Piperine is a small molecule that has been shown to destabilize the SRX in rabbit fast twitch fibers.

Biophysics of human anatomy and physiology-a Special Issue in honor of Prof. Cristobal dos Remedios on the occasion of his 80 birthday.

In 2001, Cristobal dos Remedios was made Professor of Anatomy (now emeritus) within Australia's highest-ranked university (University of Sydney). For the majority of his career, he has examined the biomechanics and biophysics of human muscle contraction. To coincide with the occasion of his 80 birthday, this Special Issue has commissioned a collection of review articles from experts exploring biophysical subjects within the general areas of human anatomy and physiology.

Nanomolar ATP binding to single myosin cross-bridges in rigor: a molecular approach to studying myosin ATP kinetics using single human cardiomyocytes.

Our knowledge in the field of cardiac muscle and associated cardiomyopathies has been evolving incrementally over the past 60 years and all was possible due to the parallel progress in techniques and methods allowing to take a fresh glimpse at an old problem. Here, we describe an exciting tool used to examine the various states of the human cardiac myosin at the single molecule level. By imaging single Alexa-ATP binding to permeabilised cardiomyocytes using total internal reflection fluorescence (TIRF) microscopy, we are able to acquire large populations of events in a short timeframe (~ 5000 sites in ~ 10 min) and measure each binding event with high spatio-temporal resolution.

Quantifying uncertainty about future antimicrobial resistance: Comparing structured expert judgment and statistical forecasting methods.

The increase of multidrug resistance and resistance to last-line antibiotics is a major global public health threat. Although surveillance programs provide useful current and historical information on the scale of the problem, the future emergence and spread of antibiotic resistance is uncertain, and quantifying this uncertainty is crucial for guiding decisions about investment in antibiotics and resistance control strategies. Mathematical and statistical models capable of projecting future rates are challenged by the paucity of data and the complexity of the emergence and spread of resistance, but experts have relevant knowledge.

Ice sheet contributions to future sea-level rise from structured expert judgment.

Despite considerable advances in process understanding, numerical modeling, and the observational record of ice sheet contributions to global mean sea-level rise (SLR) since the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change, severe limitations remain in the predictive capability of ice sheet models. As a consequence, the potential contributions of ice sheets remain the largest source of uncertainty in projecting future SLR. Here, we report the findings of a structured expert judgement study, using unique techniques for modeling correlations between inter- and intra-ice sheet processes and their tail dependences.

Piperine, an alkaloid inhibiting the super-relaxed state of myosin, binds to the myosin regulatory light chain.

Piperine, an alkaloid from black pepper, was found to inhibit the super-relaxed state (SRX) of myosin in fast-twitch skeletal muscle fibers. In this work we report that the piperine molecule binds heavy meromyosin (HMM), whereas it does not interact with the regulatory light chain (RLC)-free subfragment-1 (S1) or with control proteins from the same muscle molecular machinery, G-actin and tropomyosin. To further narrow down the location of piperine binding, we studied interactions between piperine and a fragment of skeletal myosin consisting of the full-length RLC and a fragment of the heavy chain (HCF).

Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers.

Mutations in β-cardiac myosin, the predominant motor protein for human heart contraction, can alter power output and cause cardiomyopathy. However, measurements of the intrinsic force, velocity, and ATPase activity of myosin have not provided a consistent mechanism to link mutations to muscle pathology. An alternative model posits that mutations in myosin affect the stability of a sequestered, super relaxed state (SRX) of the protein with very slow ATP hydrolysis and thereby change the number of myosin heads accessible to actin.

Oklahoma's induced seismicity strongly linked to wastewater injection depth.

The sharp rise in Oklahoma seismicity since 2009 is due to wastewater injection. The role of injection depth is an open, complex issue, yet critical for hazard assessment and regulation. We developed an advanced Bayesian network to model joint conditional dependencies between spatial, operational, and seismicity parameters.

Probabilistic reasoning about measurements of equilibrium climate sensitivity: combining disparate lines of evidence.

Where policy and science intersect, there are always issues of ambiguous and conflicting lines of evidence. Combining disparate information sources is mathematically complex; common heuristics based on simple statistical models easily lead us astray. Here, we use Bayesian Nets (BNs) to illustrate the complexity in reasoning under uncertainty.