Current state of radiomic research in pancreatic cancer: focusing on study design and reproducibility of findings.

OBJECTIVES: To critically appraise methodology and reproducibility of published studies on CT radiomics of pancreatic ductal adenocarcinoma (PDAC). METHODS: PRISMA literature search of MEDLINE, PubMed, and Scopus databases was conducted from June to August 2022 relating to CT radiomics human research articles pertaining to PDAC diagnosis, treatment, and/ or prognosis, utilising Image Biomarker Standardisation Initiative-compliant (IBSI) radiomic software. Keyword search included [pancreas OR pancreatic] AND [radiomic OR [quantitative AND imaging] OR [texture AND analysis]]. Analysis included cohort size, CT protocol used, radiomic feature (RF) extraction, segmentation, and selection, software used, outcome correlation, and statistical methodology, with focus on reproducibility. RESULTS: Initial search yielded 1112 articles; however, only 12 articles met all inclusion/exclusion criteria. Cohort sizes ranged from 37 to 352 (median = 106, mean = 155.8). CT slice thickness varied among studies (4 using ≤ 1 mm, 5 using > 1 to 3 mm, 2 using > 3 to 5 mm, 1 not specifying). CT protocol varied (5 using a single portal-venous (pv)-phase, 5 using a pancreas protocol, 1 study using a non-contrast protocol). RF extraction and segmentation were heterogeneous (RF extraction: 5 using pv-phase, 2 using late arterial, 4 using multi-phase, 1 using non-contrast phase; RF selection: 3 pre-selected, 9 software-selected). 2D/3D RF segmentation was diverse (2D in 6, 3D in 4, 2D and 3D in 2 studies). Six different radiomics software were used. Research questions and cohort characteristics varied, ultimately leading to non-comparable outcome results. CONCLUSION: The current twelve published IBSI-compliant PDAC radiomic studies show high variability and often incomplete methodology resulting in low robustness and reproducibility. CLINICAL RELEVANCE STATEMENT: Radiomics research requires IBSI compliance, data harmonisation, and reproducible feature extraction methods for non-invasive imaging biomarker discoveries to be valid. This will ensure a successful clinical implementation and ultimately an improvement of patient outcomes as part of precision and personalised medicine. KEY POINTS: • Current state of radiomics research in pancreatic cancer shows low software compliance to the Image Biomarker Standardisation Initiative (IBSI). • IBSI-compliant radiomics studies in pancreatic cancer are heterogeneous and not comparable, and the majority of study designs showed low reproducibility. • Improved methodology and standardisation of practice in the emerging field of radiomics has the potential of this non-invasive imaging biomarker in the management of pancreatic cancer.

Anticholinergic exposure and its association with dementia/Alzheimer's disease and mortality in older adults.

BACKGROUND: Use of anticholinergic (ACH) medications is associated with increased risk of cognitive decline in the elderly. However, little is known about this association from a health plan perspective. METHODS: This retrospective cohort study used the Humana Research Database to identify individuals with at least one ACH medication dispensed in 2015. Patients were followed until incidence of dementia/Alzheimer's disease, death, disenrollment or end of December 2019. Multivariate Cox regression models were used to assess the association between ACH exposure and study outcomes, adjusting for demographics and clinical characteristics. RESULTS: A total of 12,209 individuals with no prior ACH use or dementia/Alzheimer's disease diagnosis were included. As ACH polypharmacy increased (i.e., from no ACH exposure, to one, two, three, and four or more ACH medications), there was a stair-step increase in the incidence rate of dementia/Alzheimer's disease (15, 30, 46, 56 and 77 per 1,000 person-years of follow-up) and in the incidence of mortality (19, 37, 80, 115 and 159 per 1,000 person-years of follow-up). After adjusting for confounders, ACH exposure to one, two, three and four or more ACH medications was associated with a 1.6 (95% CI 1.4-1.9), 2.1 (95% CI 1.7-2.8), 2.6 (95% CI 1.5-4.4), and 2.6 (95% CI 1.1-6.3) times, respectively, increased risk of a dementia/Alzheimer's disease diagnosis compared to periods of no ACH exposure. ACH exposure to one, two, three and four or more medications was associated with a 1.4 (95% CI 1.2-1.6), 2.6 (95% CI 2.1-3.3), 3.8 (95% CI 2.6-5.4), and 3.4 (95% CI 1.8-6.4) times, respectively, increased risk of mortality compared to periods of no ACH exposure. CONCLUSIONS: Reducing ACH exposure may potentially minimize long-term adverse effects in older adults. Results suggest populations which may benefit from targeted interventions to reduce ACH polypharmacy.

Out-of-hospital cardiac arrest due to hanging: a retrospective analysis.

BACKGROUND: There has been little research into the prehospital management of cardiac arrest following hanging despite it being among the most prevalent methods of suicide worldwide. The aim of this study was to report the characteristics, resuscitative treatment and outcomes of patients managed in the prehospital environment for cardiac arrest secondary to hanging and compare these with all-cause out-of-hospital cardiac arrest (OHCA). METHODS: Data from a UK ambulance service cardiac arrest registry were extracted for all cases in which treatment was provided for OHCA due to hanging between 1 January 2013 and 30 June 2018. Cases were linked to outcome data obtained from the Trauma Audit and Research Network. Comparison of the cohort was made to previously published data from a UK study of all-cause OHCA with 95% CIs calculated for the proportional difference between the studies in selected presentation and outcome variables. RESULTS: 189 cases were identified. 95 patients were conveyed to hospital and four of these survived to discharge. 40 patients were conveyed despite absence of a spontaneous circulation and none of these patients survived. While only three patients were initially in a shockable rhythm, DC shocks were administered in 20 cases. There was one case of failed ventilation prompting front-of-neck access for oxygenation. By comparison with all-cause OHCA the proportion of patients with a spontaneous circulation at hospital handover was similar (27.0% vs 27.5%; 0.5% difference, 95% CI -5.9% to 6.8%, p=0.882) but survival to hospital discharge was significantly lower (2.2% vs 8.4%; 6.2% difference, 95% CI 4.1% to 8.3%, p=0.002). CONCLUSION: Clinical outcomes following OHCA due to hanging are poor, particularly when patients are transported while in cardiac arrest. Failure to ventilate was uncommon, and clinicians should be alert to the possibility of shockable rhythms developing during resuscitation.

Worldwide border interceptions provide a window into human-mediated global insect movement.

As part of national biosecurity programs, cargo imports, passenger baggage, and international mail are inspected at ports of entry to verify compliance with phytosanitary regulations and to intercept potentially damaging nonnative species to prevent their introduction. Detection of organisms during inspections may also provide crucial information about the species composition and relative arrival rates in invasion pathways that can inform the implementation of other biosecurity practices such as quarantines and surveillance. In most regions, insects are the main taxonomic group encountered during inspections. We gathered insect interception data from nine world regions collected from 1995 to 2019 to compare the composition of species arriving at ports in these regions. Collectively, 8,716 insect species were intercepted in these regions over the last 25 yr, with the combined international data set comprising 1,899,573 interception events, of which 863,972 were identified to species level. Rarefaction analysis indicated that interceptions comprise only a small fraction of species present in invasion pathways. Despite differences in inspection methodologies, as well as differences in the composition of import source regions and imported commodities, we found strong positive correlations in species interception frequencies between regions, particularly within the Hemiptera and Thysanoptera. There were also significant differences in species frequencies among insects intercepted in different regions. Nevertheless, integrating interception data among multiple regions would be valuable for estimating invasion risks for insect species with high likelihoods of introduction as well as for identifying rare but potentially damaging species.

You can['t] catch the sun in a net!: Children's misinterpretations of educational science television.

Many science television shows feature refutation narratives where characters speculate about the value of scientific misconceptions (e.g., the sun circles the earth) before learning factual information. Previous research suggests that young children misunderstand these stories, and the current study examined whether learning could be improved using interventions previously validated with adults. Children (N = 201) aged 4-7 years viewed a refutation narrative in its original form or in a modified format that lacked misconceptions or that contextualized those misconceptions with additional scaffolds. Although children's comprehension of factual information was high across all conditions, their understanding of misconceptions depended on their prior knowledge. Specifically, children with low prior knowledge mistakenly identified misconceptions as intended factual lessons unless they viewed the story without misconceptions or with two forms of additional scaffolding. Conversely, children with high prior knowledge understood the original story best. These findings suggest that the inclusion of fantasy ideas in children's science programming can disrupt learning for certain children and bolster learning for others.

Considering unseen arrivals in predictions of establishment risk based on border biosecurity interceptions.

Assessing species establishment risk is an important task used for informing biosecurity activities aimed at preventing biological invasions. Propagule pressure is a major contributor to the probability of invading species establishment; however, direct assessment of numbers of individuals arriving is virtually never possible. Inspections conducted at borders by biosecurity officials record counts of species (or higher-level taxa) intercepted during inspections, which can be used as proxies for arrival rates. Such data may therefore be useful for predicting species establishments, though some species may establish despite never being intercepted. We present a stochastic process-based model of the arrival-interception-establishment process to predict species establishment risk from interception count data. The model can be used to estimate the probability of establishment, both for species that were intercepted and species that had no interceptions during a given observation period. We fit the stochastic model to data on two insect families, Cerambycidae and Aphididae, that were intercepted and/or established in the United States or New Zealand. We also explore the effects of variation in model parameters and the inclusion of an Allee effect in the establishment probability. Although interception data sets contain much noise due to variation in inspection policy, interception effort and among-species differences in detectability, our study shows that it is possible to use such data for predicting establishments and distinguishing differences in establishment risk profile between taxonomic groups. Our model provides a method for predicting the number of species that have breached border biosecurity, including both species detected during inspections but also "unseen arrivals" that have never been intercepted, but have not yet established a viable population. These estimates could inform prioritization of different taxonomic groups, pathways or identification effort in biosecurity programs.

Efficient and Tunable White-Light Emission Using a Dispersible Porous Polymer.

A dispersible porous polymer (PEG113 -b-DVB800 -co-AA200 ) based on the controlled radical polymerization of divinylbenzene and acrylic acid with a poly(ethylene glycol) (PEG) macrochain transfer agent (macro-CTA) is synthesized and postsynthetically modified with anthracene. This blue-emitting porous polymer is used to encapsulate the yellow-emitting fluorophore rhodamine B into its core, resulting in a white-light emitting dispersion with a quantum yield of 38% and commission internationale de l'éclairage coordinates of (X = 0.33, Y = 0.32).

Limiting Effect of Self-Shading on the Height of Tradescantia fluminensis Mats.

Tradescantia fluminensis is an invasive plant species in New Zealand, Australia and parts of the USA. It reproduces vegetatively and can grow to form dense mats up to 60 cm deep. Growth is limited by available light, and shading is one of the few effective methods of control. In this paper, we develop a dynamic model of a vertical cross section of a T. fluminensis mat, capturing vertical variation in its biomass and internal light intensity. We measure both variables at different heights in experimental mats of the species and use these data to parameterize the model. The model produces realistic vertical biomass and light intensity profiles. We show that the mat grows to a steady-state biomass that depends only on: (i) the light absorption coefficient, which we estimate from experimental data and (ii) the ratio of photosynthesis to respiration rate. This steady state undergoes a transcritical bifurcation; when the ambient light intensity falls below a critical level, the biomass shrinks to zero and the mat cannot survive.

Disentangling nestedness from models of ecological complexity.

Complex networks of interactions are ubiquitous and are particularly important in ecological communities, in which large numbers of species exhibit negative (for example, competition or predation) and positive (for example, mutualism) interactions with one another. Nestedness in mutualistic ecological networks is the tendency for ecological specialists to interact with a subset of species that also interact with more generalist species. Recent mathematical and computational analysis has suggested that such nestedness increases species richness. By examining previous results and applying computational approaches to 59 empirical data sets representing mutualistic plant­pollinator networks, we show that this statement is incorrect. A simpler metric­the number of mutualistic partners a species has­is a much better predictor of individual species survival and hence, community persistence. Nestedness is, at best, a secondary covariate rather than a causative factor for biodiversity in mutualistic communities. Analysis of complex networks should be accompanied by analysis of simpler, underpinning mechanisms that drive multiple higher-order network properties.

An efficient method to estimate the optimum regularization parameter in RLDA.

MOTIVATION: The biomarker discovery process in high-throughput genomic profiles has presented the statistical learning community with a challenging problem, namely learning when the number of variables is comparable or exceeding the sample size. In these settings, many classical techniques including linear discriminant analysis (LDA) falter. Poor performance of LDA is attributed to the ill-conditioned nature of sample covariance matrix when the dimension and sample size are comparable. To alleviate this problem, regularized LDA (RLDA) has been classically proposed in which the sample covariance matrix is replaced by its ridge estimate. However, the performance of RLDA depends heavily on the regularization parameter used in the ridge estimate of sample covariance matrix. RESULTS: We propose a range-search technique for efficient estimation of the optimum regularization parameter. Using an extensive set of simulations based on synthetic and gene expression microarray data, we demonstrate the robustness of the proposed technique to Gaussianity, an assumption used in developing the core estimator. We compare the performance of the technique in terms of accuracy and efficiency with classical techniques for estimating the regularization parameter. In terms of accuracy, the results indicate that the proposed method vastly improves on similar techniques that use classical plug-in estimator. In that respect, it is better or comparable to cross-validation-based search strategies while, depending on the sample size and dimensionality, being tens to hundreds of times faster to compute. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/danik0411/optimum-rlda CONTACT: amin.zollanvari@nu.edu.kzSupplementary information: Supplementary materials are available at Bioinformatics online.

How Herbivore Browsing Strategy Affects Whole-Plant Photosynthetic Capacity.

If a browse damage index indicates that a tree has been 50% browsed by herbivores, does this mean half the leaves are entirely eaten or are all the leaves half eaten? Were the affected leaves old or young? Large or small? In sunshine or shade? Understanding what effect browsing will have on the photosynthetic capacity and the plant's survival ability clearly requires a greater understanding of browsing strategy across the canopy than can be given by a single index value. We developed stochastic models of leaf production, growth and consumption using data from kamahi (Weinmannia racemosa) trees in New Zealand which have been browsed by possums (Trichosurus vulpecula), to ascertain which of six feasible browsing strategies possums are most likely to be employing. We compared the area distribution of real fallen leaves to model output in order to select the best model, and used the model to predict the age distribution of leaves on the tree and thus infer its photosynthetic capability. The most likely browsing strategy that possums employ on kamahi trees is a preference for virgin (i.e. previously unbrowsed) leaves, consistent with the idea that browsing increases the production of chemical plant defences. More generally, our results show that herbivore browsing strategy can significantly change the whole-plant photosynthetic capability of any plant and hence its ability to survive, and therefore, herbivore damage indices should be used in conjunction with more detailed information about herbivore browsing strategy.

Evolutionarily Stable Strategies for Fecundity and Swimming Speed of Fish.

Many pelagic fish species have a life history that involves producing a large number of small eggs. This is the result of a trade-off between fecundity and larval survival probability. There are also trade-offs involving other traits, such as larval swimming speed. Swimming faster increases the average food encounter rate but also increases the metabolic cost. Here we introduce an evolutionary model comprising fecundity and swimming speed as heritable traits. We show that there can be two evolutionary stable strategies. In environments where there is little noise in the food encounter rate, the stable strategy is a low-fecundity strategy with a swimming speed that minimises the mean time taken to reach reproductive maturity. However, in noisy environments, for example where the prey distribution is patchy or the water is turbulent, strategies that optimise mean outcomes are often outperformed by strategies that increase inter-individual variance. We show that, when larval growth rates are unpredictable, a high-fecundity strategy is evolutionarily stable. In a population following this strategy, the swimming speed is higher than would be anticipated by maximising the mean growth rate.

Collective Cell Behaviour with Neighbour-Dependent Proliferation, Death and Directional Bias.

Collective cell migration and proliferation are integral to tissue repair, embryonic development, the immune response and cancer. Central to collective cell migration and proliferation are interactions among neighbouring cells, such as volume exclusion, contact inhibition and adhesion. These individual-level processes can have important effects on population-level outcomes, such as growth rate and equilibrium density. We develop an individual-based model of cell migration and proliferation that includes these interactions. This is an extension of a previous model with neighbour-dependent directional bias to incorporate neighbour-dependent proliferation and death. A deterministic approximation to this individual-based model is derived using a spatial moment dynamics approach, which retains information about the spatial structure of the cell population. We show that the individual-based model and spatial moment model match well across a range of parameter values. The spatial moment model allows insight into the two-way interaction between spatial structure and population dynamics that cannot be captured by traditional mean-field models.

In the blink of an eye: relating positive-feedback sensitivity to striatal dopamine D2-like receptors through blink rate.

For >30 years, positron emission tomography (PET) has proven to be a powerful approach for measuring aspects of dopaminergic transmission in the living human brain; this technique has revealed important relationships between dopamine D2-like receptors and dimensions of normal behavior, such as human impulsivity, and psychopathology, particularly behavioral addictions. Nevertheless, PET is an indirect estimate that lacks cellular and functional resolution and, in some cases, is not entirely pharmacologically specific. To identify the relationships between PET estimates of D2-like receptor availability and direct in vitro measures of receptor number, affinity, and function, we conducted neuroimaging and behavioral and molecular pharmacological assessments in a group of adult male vervet monkeys. Data gathered from these studies indicate that variation in D2-like receptor PET measurements is related to reversal-learning performance and sensitivity to positive feedback and is associated with in vitro estimates of the density of functional dopamine D2-like receptors. Furthermore, we report that a simple behavioral measure, eyeblink rate, reveals novel and crucial links between neuroimaging assessments and in vitro measures of dopamine D2 receptors.

Constructing random matrices to represent real ecosystems.

Models of complex systems with n components typically have order n(2) parameters because each component can potentially interact with every other. When it is impractical to measure these parameters, one may choose random parameter values and study the emergent statistical properties at the system level. Many influential results in theoretical ecology have been derived from two key assumptions: that species interact with random partners at random intensities and that intraspecific competition is comparable between species. Under these assumptions, community dynamics can be described by a community matrix that is often amenable to mathematical analysis. We combine empirical data with mathematical theory to show that both of these assumptions lead to results that must be interpreted with caution. We examine 21 empirically derived community matrices constructed using three established, independent methods. The empirically derived systems are more stable by orders of magnitude than results from random matrices. This consistent disparity is not explained by existing results on predator-prey interactions. We investigate the key properties of empirical community matrices that distinguish them from random matrices. We show that network topology is less important than the relationship between a species' trophic position within the food web and its interaction strengths. We identify key features of empirical networks that must be preserved if random matrix models are to capture the features of real ecosystems.

Scaling laws of marine predator search behaviour.

Many free-ranging predators have to make foraging decisions with little, if any, knowledge of present resource distribution and availability. The optimal search strategy they should use to maximize encounter rates with prey in heterogeneous natural environments remains a largely unresolved issue in ecology. Lévy walks are specialized random walks giving rise to fractal movement trajectories that may represent an optimal solution for searching complex landscapes. However, the adaptive significance of this putative strategy in response to natural prey distributions remains untested. Here we analyse over a million movement displacements recorded from animal-attached electronic tags to show that diverse marine predators-sharks, bony fishes, sea turtles and penguins-exhibit Lévy-walk-like behaviour close to a theoretical optimum. Prey density distributions also display Lévy-like fractal patterns, suggesting response movements by predators to prey distributions. Simulations show that predators have higher encounter rates when adopting Lévy-type foraging in natural-like prey fields compared with purely random landscapes. This is consistent with the hypothesis that observed search patterns are adapted to observed statistical patterns of the landscape. This may explain why Lévy-like behaviour seems to be widespread among diverse organisms, from microbes to humans, as a 'rule' that evolved in response to patchy resource distributions.

Low-Power Analog Integrated Architecture of the Voting Classification Algorithm for Diabetes Disease Prediction.

A low-power (∼ 600nW), fully analog integrated architecture for a voting classification algorithm is introduced. It can effectively handle multiple-input features, maintaining exceptional levels of accuracy and with very low power consumption. The proposed architecture is based on a versatile Voting algorithm that selectively incorporates one of three key classification models: Bayes or Centroid, or, the Learning Vector Quantization model; all of which are implemented using Gaussian-likelihood and Euclidean distance function circuits, as well as a current comparison circuit. To evaluate the proposed architecture, a comprehensive comparison with popular analog classifiers is performed, using real-life diabetes dataset. All model architectures were trained using Python and compared with the software-based classifiers. The circuit implementations were performed using the TSMC 90 nm CMOS process technology and the Cadence IC Suite was utilized for the design, schematic and post-layout simulations. The proposed classifiers achieved sensitivity of ≥ 96.7% and specificity of ≥ 89.7%.

Dysregulation of D2-mediated dopamine transmission in monkeys after chronic escalating methamphetamine exposure.

Compulsive drug-seeking and drug-taking are important substance-abuse behaviors that have been linked to alterations in dopaminergic neurotransmission and to impaired inhibitory control. Evidence supports the notions that abnormal D2 receptor-mediated dopamine transmission and inhibitory control may be heritable risk factors for addictions, and that they also reflect drug-induced neuroadaptations. To provide a mechanistic explanation for the drug-induced emergence of inhibitory-control deficits, this study examined how a chronic, escalating-dose regimen of methamphetamine administration affected dopaminergic neurochemistry and cognition in monkeys. Dopamine D2-like receptor and dopamine transporter (DAT) availability and reversal-learning performance were measured before and after exposure to methamphetamine (or saline), and brain dopamine levels were assayed at the conclusion of the study. Exposure to methamphetamine reduced dopamine D2-like receptor and DAT availability and produced transient, selective impairments in the reversal of a stimulus-outcome association. Furthermore, individual differences in the change in D2-like receptor availability in the striatum were related to the change in response to positive feedback. These data provide evidence that chronic, escalating-dose methamphetamine administration alters the dopamine system in a manner similar to that observed in methamphetamine-dependent humans. They also implicate alterations in positive-feedback sensitivity associated with D2-like receptor dysfunction as the mechanism by which inhibitory control deficits emerge in stimulant-dependent individuals. Finally, a significant degree of neurochemical and behavioral variation in response to methamphetamine was detected, indicating that individual differences affect the degree to which drugs of abuse alter these processes. Identification of these factors ultimately may assist in the development of individualized treatments for substance dependence.

Of mast and mean: differential-temperature cue makes mast seeding insensitive to climate change.

Mast-seeding plants often produce high seed crops the year after a warm spring or summer, but the warm-temperature model has inconsistent predictive ability. Here, we show for 26 long-term data sets from five plant families that the temperature difference between the two previous summers (ΔT) better predicts seed crops. This discovery explains how masting species tailor their flowering patterns to sites across altitudinal temperature gradients; predicts that masting will be unaffected by increasing mean temperatures under climate change; improves prediction of impacts on seed consumers; demonstrates that strongly masting species are hypersensitive to climate; explains the rarity of consecutive high-seed years without invoking resource constraints; and generates hypotheses about physiological mechanisms in plants and insect seed predators. For plants, ΔT has many attributes of an ideal cue. This temperature-difference model clarifies our understanding of mast seeding under environmental change, and could also be applied to other cues, such as rainfall.