Digital Commons Network^™

Multifocal, Multiphenotypic Tumours Arising From An Mtor Mutation Acquired In Early Embryogenesis, Clarissa N Pacyna, Madhanagopal Anandapadamanaban, Kevin W Loudon, Iain M Hay, Olga Perisic, Matthew Byrne, Kirsty Roberts, Yvette Hooks, Anne Y Warren, Grant D Stewart, Menna R Clatworthy, Sarah A Teichmann, Sam Behjati, Peter J Campbell, Roger L Williams, Thomas J Mitchell

Faculty, Staff and Student Publications

Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing. Phylogenetic reconstruction timed the origin of all tumours to a multipotent embryonic cell committed to the right kidney, around 4 weeks post-conception. Biochemical and structural analysis of their shared MTOR mutation, absent from normal tissues, demonstrates enhanced protein flexibility, enabling a FAT domain hinge to dramatically increase activity of mTORC1 and mTORC2. …

Exploring Age And Gender Disparities In Cardiometabolic Phenotypes And Lipidomic Signatures Among Chinese Adults: A Nationwide Cohort Study, Xiaojing Jia, Hong Lin, Ruizhi Zheng, Shuangyuan Wang, Yilan Ding, Mian Li, Min Xu, Guixia Wang, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Jie Zheng, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Shenghan Lai, Donghui Li, Weiguo Hu, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu, 4c Study Group

Faculty, Staff and Student Publications

Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China. Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata, particularly for dyslipidemia and its components. Generalized additive models were employed to characterize phenotype features, elucidating how gender differences evolve with advancing age. Half of the 16 phenotypes consistently exhibited no sex differences, while …

Molecular Architecture And Functional Dynamics Of The Pre-Incision Complex In Nucleotide Excision Repair, Jina Yu, Chunli Yan, Tanmoy Paul, Lucas Brewer, Susan E Tsutakawa, Samir M Hamdan, Ivaylo Ivanov

Faculty, Staff and Student Publications

Nucleotide excision repair (NER) is vital for genome integrity. Yet, our understanding of the complex NER protein machinery remains incomplete. Combining cryo-EM and XL-MS data with AlphaFold2 predictions, we build an integrative model of the NER pre-incision complex(PInC). Here TFIIH serves as a molecular ruler, defining the DNA bubble size and precisely positioning the XPG and XPF nucleases for incision. Using simulations and graph theoretical analyses, we unveil PInC's assembly, global motions, and partitioning into dynamic communities. Remarkably, XPG caps XPD's DNA-binding groove and bridges both junctions of the DNA bubble, suggesting a novel coordination mechanism of PInC's dual incision. …

Meta-Analysis Of Censored Adverse Events, Xinyue Qi, Shouhao Zhou, Christine B Peterson, Yucai Wang, Xinying Fang, Chan Shen

Faculty, Staff and Student Publications

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete reporting of adverse events (AEs) in published clinical studies is frequently encountered, especially if the observed number of AEs is below a pre-specified study-dependent threshold. Ignoring the censored AE information, often found in lower frequency, can significantly bias the estimated incidence rate of AEs. Despite its importance, this prevalent issue in meta-analysis has received little statistical or analytic attention in the literature. To address this challenge, we propose a Bayesian …

Unlocking Ferroptosis In Prostate Cancer – The Road To Novel Therapies And Imaging Markers, Pham Hong Anh Cao, Abishai Dominic, Fabiola Ester Lujan, Sanjanaa Senthilkumar, Pratip K Bhattacharya, Elavarasan Subramani

Faculty, Staff and Student Publications

Ferroptosis is a distinct form of regulated cell death that is predominantly driven by the build-up of intracellular iron and lipid peroxides. Ferroptosis suppression is widely accepted to contribute to the pathogenesis of several tumours including prostate cancer. Results from some studies reported that prostate cancer cells can be highly susceptible to ferroptosis inducers, providing potential for an interesting new avenue of therapeutic intervention for advanced prostate cancer. In this Perspective, we describe novel molecular underpinnings and metabolic drivers of ferroptosis, analyse the functions and mechanisms of ferroptosis in tumours, and highlight prostate cancer-specific susceptibilities to ferroptosis by connecting ferroptosis …

A Scoping Review Of Rule-Based Clinical Decision Support Malfunctions, Deevakar Rogith, Adam Wright

Faculty, Staff and Student Publications

Objective: Conduct a scoping review of research studies that describe rule-based clinical decision support (CDS) malfunctions.

Materials and methods: In April 2022, we searched three bibliographic databases (MEDLINE, CINAHL, and Embase) for literature referencing CDS malfunctions. We coded the identified malfunctions according to an existing CDS malfunction taxonomy and added new categories for factors not already captured. We also extracted and summarized information related to the CDS system, such as architecture, data source, and data format.

Results: Twenty-eight articles met inclusion criteria, capturing 130 malfunctions. Architectures used included stand-alone systems (eg, web-based calculator), integrated systems (eg, best practices alerts), and …

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Andrew J Jang, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Ketamine For Acute Pain After Trauma: A Pragmatic, Randomized Clinical Trial, James M Klugh, Thaddeus J Puzio, Michael W Wandling, Chelsea J Guy-Frank, Charles Green, Paulina B Sergot, Samuel J Prater, Julius Balogh, Christopher T Stephens, Charles E Wade, Lillian S Kao, John A Harvin

Faculty, Staff and Student Publications

Background: Non-narcotic intravenous medications may be a beneficial adjunct to oral multimodal pain regimens (MMPRs) which reduce but do not eliminate opioid exposure and prescribing after trauma. We hypothesized that the addition of a subdissociative ketamine infusion (KI) to a standardized oral MMPR reduces inpatient opioid exposure.

Methods: Eligible adult trauma patients admitted to the intermediate or intensive care unit were randomized upon admission to our institutional MMPR per usual care (UC) or UC plus subdissociative KI for 24 hours to 72 hours after arrival. The primary outcome was morphine milligram equivalents per day (MME/d) and secondary outcomes included total …

Lhcgr Inactivating Variants: Single Center Experience And Systematic Review Of Phenotype-Genotype Of 46, Xy And 46, Xx Patients, Rohit Barnabas, Swati Jadhav, Anurag Ranjan Lila, Sirisha Kusuma Boddu, Saba Samad Memon, Sneha Arya, Samiksha Chandrashekhar Hegishte, Manjiri Karlekar, Virendra A Patil, Vijaya Sarathi, Nalini S Shah, Tushar Bandgar

Faculty, Staff and Student Publications

Background: The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series.

Methods: We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described.

Results: Three 46,XY patients (age 6-18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Andrew J Jang, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

The Case For Eliminating Excessive Worry As A Requirement For Generalized Anxiety Disorder: A Cross-National Investigation, Ayelet Meron Ruscio, Madeleine Rassaby, Murray Stein, Dan Stein, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Jordi Alonso, Lukoye Atwoli, Guilherme Borges, Evelyn Bromet

Internal Medicine, East Africa

Background: Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not ‘excessive’ relative to the context. We carried out the first largescale, cross-national study to explore the implications of removing this excessiveness requirement.

Methods: Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 …

Data Provenance Via Differential Auditing, Xin Mu, Ming Pang, Feida Zhu

Research Collection School Of Computing and Information Systems

With the rising awareness of data assets, data governance, which is to understand where data comes from, how it is collected, and how it is used, has been assuming evergrowing importance. One critical component of data governance gaining increasing attention is auditing machine learning models to determine if specific data has been used for training. Existing auditing techniques, like shadow auditing methods, have shown feasibility under specific conditions such as having access to label information and knowledge of training protocols. However, these conditions are often not met in most real-world applications. In this paper, we introduce a practical framework for …

Latent Representation Learning For Geospatial Entities, Ween Jiann Lee, Hady Wirawan Lauw

Research Collection School Of Computing and Information Systems

Representation learning has been instrumental in the success of machine learning, offering compact and performant data representations for diverse downstream tasks. In the spatial domain, it has been pivotal in extracting latent patterns from various data types, including points, polylines, polygons, and networked structures. However, existing approaches often fall short of explicitly capturing both semantic and spatial information, relying on proxies and synthetic features. This article presents GeoNN, a novel graph neural network-based model designed to learn spatially-aware embeddings for geospatial entities. GeoNN leverages edge features generated from geodesic functions, dynamically selecting relevant features based on relative locations. It introduces …

Nigerian Software Engineer Or American Data Scientist? Github Profile Recruitment Bias In Large Language Models, Takashi Nakano, Kazumasa Shimari, Raula Gaikovina Kula, Christoph Treude, Marc Cheong, Kenichi Matsumoto

Research Collection School Of Computing and Information Systems

Large Language Models (LLMs) have taken the world by storm, demonstrating their ability not only to automate tedious tasks, but also to show some degree of proficiency in completing software engineering tasks. A key concern with LLMs is their “black-box” nature, which obscures their internal workings and could lead to societal biases in their outputs. In the software engineering context, in this early results paper, we empirically explore how well LLMs can automate recruitment tasks for a geographically diverse software team. We use OpenAI's ChatGPT to conduct an initial set of experiments using GitHub User Profiles from four regions to …

Kpiroot: Efficient Monitoring Metric-Based Root Cause Localization In Large-Scale Cloud Systems, Wenwei Gu, Xinying Sun, Jinyang Liu, Yintong Huo, Zhuangbin Chen, Jianping Zhang, Jiazhen Gu, Yongqiang Yang, Michael R. Lyu

Research Collection School Of Computing and Information Systems

To ensure the reliability of cloud systems, their run-time status reflecting the service quality is periodically monitored with monitoring metrics, i.e., KPIs (key performance indicators). When performance issues happen, root cause localization pinpoints the specific KPIs that are responsible for the degradation of overall service quality, facilitating prompt problem diagnosis and resolution. To this end, existing methods generally locate root-cause KPIs by identifying the KPIs that exhibit a similar anomalous trend to the overall service performance. While straightforward, solely relying on the similarity calculation may be ineffective when dealing with cloud systems with complicated interdependent services. Recent deep learning-based methods …

What Is The Fallacy Of Approximation?, Matthew Hammerton, Sovan Patra

Research Collection School of Social Sciences

Many philosophers appeal to the “fallacy of approximation”, or “problem of second best”. However, despite the pervasiveness of such appeals, there has been only a single attempt to provide a systematic account of what the fallacy is. We identify the shortcomings of this account and propose a better one in its place. Our account not only captures all the contexts in which approximation-based reasoning occurs but also systematically explains the several different ways in which it can be in error.

Towards An Extended Resource Theory Of Marital Power: Parental Education And Household Decision-Making In Rural China, Cheng Cheng, Yu Xie

Research Collection School of Social Sciences

Existing literature on the resource theory of marital power has focused on the relative resources of spouses and overlooked the resource contributions of spouses’ extended families. We propose an extended resource theory that considers how the comparative resources of a couple’s natal families are directly associated with marital power, net of the comparative resources of the couple. Using data from the China Panel Family Studies, we examine how the relative education of a couple’s respective parents affects the wife’s decision-making power, net of the relative education of the couple. Results suggest that the higher the wife’s parental education relative to …

A Quantitative Study Assessing The Impact Of Financial Sector Safeguards Rules On Us Publicly Traded Companies' Cybersecurity Breach Frequency And Severity, Alan Dinerman

School of Public Service Theses & Dissertations

Cybersecurity failure in the private sector is a growing federal policy priority. Nevertheless, US policy makers struggle with policy instrumentation in this domain. Behavioral public policy theory asserts that a linkage exists between policy target behavioral & cultural attributes and effective policy tool instrumentation. The federal government is now embracing a regulation heavy approach, but little empirical study exists at the nexus of behavioral public policy theory and use of regulatory tools in the cybersecurity policy domain. Since the early 2000s, the financial sector has employed a regulation heavy approach using the Safeguards regulations to facilitate cybersecurity in financial private …

Short-Semester Courses: Mitigating Unfavorable Precollege Issues For Students At A Technical College, James T. Moore Jr.

Educational Leadership & Workforce Development Theses & Dissertations

Technical colleges serve a distinct student population and provide an open access point to higher education for students not wishing to attend a university. Graduation and retention rates continue to demonstrate a gap between what technical colleges wish to achieve and the actual achievement. Technical college leaders continue to embrace policies and programs intended to support students at university system schools and which poorly serve the needs of technical college students. As a result, little is known about the lived experiences of technical college students. Data were collected through a six individual semi-structured interview. The six participants of the study …

Literacy Leadership: Power In The Discourse Of Learning, Melissa Guinn Crawley Twisdale

Educational Leadership & Workforce Development Theses & Dissertations

The phenomenon of teacher learning, especially within literacy education pedagogy, has rarely been a topic of educational research. The nature of ongoing teacher learning is as challenging to study as student learning in that, learning in and of itself is not widely defined in the educational research literature. Equally challenging is the topic of literacy for which there are numerous and varying definitions, many of which carry political and controversial connotations (Aukerman & Schuldt, 2021). The term science of reading, for example, often carries an intensive focus on assessed reading proficiency as the primary goal of reading instruction, although the …

Institutional Pressures On School Leadership And Innovation After Pandemic-Related School Closures: A Phenomenological Study, Gary Eugene Skeen

Educational Leadership & Workforce Development Theses & Dissertations

The COVID-19 pandemic was a phenomenon that caused immediate change to global institutions, including education. As schools created new systems during the pandemic, as restrictions began to be eased, many divisions felt pressure to continue virtual options after schools fully reopened to students. This pressure influenced the decisions made by school leaders, with internal and external pressures dictating how leaders navigated the decisions made regarding virtual learning after pandemic-related school closures. In the presence of the widespread phenomenon of the pandemic, school leaders faced pressures to reimagine learning through innovation or revert to institutional structures normalized prior to pandemic closures. …

The Role Of Policy Entrepreneurs In Understanding Oral Health Care Policy: A Case Study Approach Analyzing Multiple Streams Framework In Nc Oral Health Policy, Lori Gordon Hendrick

School of Public Service Theses & Dissertations

The United States Surgeon General has defined oral diseases as a “silent epidemic” that affects the most vulnerable citizens. More often, this includes those from low socio-economic backgrounds, children, elderly, and many members of ethnic minority groups. Although preventative and treatment modalities have improved over the past fifty years, some Americans continue to have little to no access to educational and preventative programs. The lack of access to dental care for all ages and oral health care literacy remains one of the largest health concerns for American citizens making it a “wicked problem”. Historically, raising Medicaid enrollment has failed to …

Cultivating Self-Knowledge In The Writing Classroom: A Study Of Contemplative Pedagogy, Jared Featherstone

English Theses & Dissertations

This pedagogical research study examines the effects of Understanding the Self Through Writing and Rhetoric, an undergraduate course designed by the researcher, on students. The course is an example of contemplative writing pedagogy, one that seeks to foreground first-person direct experience of the subject matter and integrates mindfulness meditation and journaling throughout. While writing and rhetoric are common undergraduate subjects to teach, the course focuses on particular, lesser-known aspects of them, internal rhetoric and self-making narrative. A third important part of the course is the examination of how communication technologies, especially social media and messaging applications, affect one’s internal rhetoric …

Optical Investigation Of A Low-Pressure Plasma In A Superconducting Radio-Frequency Cavity, Zachary A. Caudell

Electrical & Computer Engineering Theses & Dissertations

The state-of-the-art cryomodules for particle accelerators use superconducting radio-frequency (SRF) cavities. It is known that accumulation of hydrocarbon impurities reduces the cavity surface work function, decreasing cryomodule performance metrics such as field emission, thermal stability, and accelerating gradients. An in-situ method of plasma processing has recently been developed to clean the cavities and restore cryomodule performance [1]. This study is to understand the properties of the low-pressure plasmas generated in a C100 SRF cavity and ultimately to improve the performance of plasma surface cleaning using optical emission spectroscopy. Using a 500 mm focal length Czerny-Turner monochromator coupled with a photomultiplier …

Comprehensive Study Of Energy Capturing, Conversion, And Transportation Behaviors In A Piezoelectric Vibration Energy Harvesting System, Bingqi Zhao

Mechanical & Aerospace Engineering Theses & Dissertations

Piezoelectric vibration energy harvester (PEH) is one of the hottest research areas to address renewable energy issues with over 10,000 journal articles published in the last two decades. However, several critical issues, such as the proof mass effects, electrical impedance, mechanical resonance, and energy charging processing, remain open. This dissertation presents a comprehensive study addressing the above issues.

To obtain reliable results, a professional quality flextensional PEH (FPEH) and multiple comprehensive experimental methods were developed, and ANSYS FEM modelling was used. Study of the proof mass effect indicated that the generated voltage linearly increased with the weight ratio of the …

Simulating The Compound Impacts Of Climate Change And Sea-Level Rise On Coastal Shallow Groundwater Using An Integrated Surface-Subsurface Hydrologic Model, Zhaoyi Cai

Civil & Environmental Engineering Theses & Dissertations

As climate change intensifies and sea levels rise, coastal aquifers become increasingly vulnerable to interacting oceanic and terrestrial processes. This dissertation examines the combined impacts of climate change and sea-level rise (SLR) on coastal shallow groundwater using an integrated surface-subsurface hydrologic model, focusing on the low-lying Little Creek watershed (LCW) in Norfolk, Virginia. The SWAT-MODFLOW model, a coupled system, unifies land surface, streamflow, and groundwater processes, providing a comprehensive framework for watershed-aquifer analysis. Model parameters were derived from U.S. Geological Survey datasets, relevant literature, station records, and technical reports, followed by meticulous calibration. The validated model first simulated baseline groundwater …

Computer Based Modeling For Small E-Vtol Propeller Performance, Ege Konuk

Mechanical & Aerospace Engineering Theses & Dissertations

The emerging field of urban air mobility (UAM) offers a novel transportation method for civil, commercial, and military applications. Vertical take-off and landing (VTOL) configurations present challenges for performance prediction during crucial flight operations. An advanced computational framework for predicting propeller performance in electric vertical takeoff and landing (eVTOL) aircraft during transition flight is essential for future concept designs. This research extends the Blade Element Momentum Theory (BEMT) to model propeller behavior at high incidence angles, crucial for eVTOL operation.

The study begins with a review of tilt-wing/rotor configurations for eVTOLs and tackles the complex aerodynamic phenomena associated with rotors …

Institutional Responses To The First Amendment: Inclusivity And The Protection Of Free Speech Rights On Campus, Christina Lipuma

Educational Leadership & Workforce Development Theses & Dissertations

This collective case study explores institutional responses to First Amendment events to determine how institutional policies impact a sense of inclusivity and the protection of free speech rights on public college and university campuses. This study identifies the practices of a sample of public, university campuses that have experienced a free speech incident to determine how the experience shaped their policies on free speech, how administrators describe their experiences following the incident, and how institutional leaders rate the outcome of their efforts in relation to balancing inclusivity in the campus environment. Due to the complex nature of public university campuses, …

An Examination Of Food And Alcohol Disturbance Based On Sexual Orientation In A Sample Of Women Who Binge Eat, Alicia M. Moulder

Psychology Theses & Dissertations

Food and alcohol disturbance (FAD), characterized by disordered eating behaviors in the context of drinking alcohol to enhance intoxication, counteract alcohol’s calories, or both, is associated with increased risk of negative drinking consequences. Previously established as a phenomenon occurring in college students, research has begun to support that FAD may also occur in nonstudents. Three particularly vulnerable groups for FAD may include women, individuals with history of binge eating, as well as sexual minority individuals. Consequently, the goals of the current study were to elucidate differences in FAD engagement between sexual minority women (SMW) and heterosexual women using a sample …

A Systems Theory-Based Framework For Uncertainty In Complex System Governance, Teresa Anne Crater

Engineering Management & Systems Engineering Theses & Dissertations

Complex systems are all around. A complex system is a system whose collective behavior is more than the behavior exhibited by the individual parts. Such a system is characterized by an exponential increase in information, complexity, ambiguity, emergence, and high levels of uncertainty (Jaradat, 2015). Uncertainty is intrinsic to complex systems. Uncertainty refers to epistemic situations involving imperfect or unknown information. Uncertainty can refer to the chance of certain anticipated outcomes occurring, or it can refer to the unknown events that are not foreseeable as to when or if one might occur. It applies to predictions of future events, to …