TREEOME: A framework for epigenetic and transcriptomic data integration to explore regulatory interactions controlling transcription

Motivation: Predictive modelling of gene expression is a powerful framework for the in silico exploration of transcriptional regulatory interactions through the integration of high-throughput -omics data. A major limitation of previous approaches is their inability to handle conditional and synergistic interactions that emerge when collectively analysing genes subject to different regulatory mechanisms. This limitation reduces overall predictive power and thus the reliability of downstream biological inference. Results: We introduce an analytical modelling framework (TREEOME: tree of models of expression) that integrates epigenetic and transcriptomic data by separating genes into putative regulatory classes. Current predictive modelling approaches have found both DNA methylation and histone modification epigenetic data to provide little or no improvement in accuracy of prediction of transcript abundance despite, for example, distinct anti-correlation between mRNA levels and promoter-localised DNA methylation. To improve on this, in TREEOME we evaluate four possible methods of formulating gene-level DNA methylation metrics, which provide a foundation for identifying gene-level methylation events and subsequent differential analysis, whereas most previous techniques operate at the level of individual CpG dinucleotides. We demonstrate TREEOME by integrating gene-level DNA methylation (bisulfite-seq) and histone modification (ChIP-seq) data to accurately predict genome-wide mRNA transcript abundance (RNA-seq) for H1-hESC and GM12878 cell lines. Availability: TREEOME is implemented using open-source software and made available as a pre-configured bootable reference environment. All scripts and data presented in this study are available online at http://sourceforge.net/projects/budden2015treeome/.Comment: 14 pages, 6 figure

Optimizing the sensitivity of high repetition rate broadband transient optical spectroscopy with modified shot-to-shot detection

A major limitation of transient optical spectroscopy is that relatively high laser fluences are required to enable broadband, multichannel detection with acceptable signal-to-noise levels. Under typical experimental conditions, many condensed phase and nanoscale materials exhibit fluence dependent dynamics, including higher order effects such as carrier-carrier annihilation. With the proliferation of commercial laser systems, offering both high repetition rates and high pulse energies, has come new opportunities for high sensitivity pump-probe measurements at low pump fluences. However, experimental considerations needed to fully leverage the statistical advantage of these laser systems has not been fully described. Here we demonstrate a high repetition rate, broadband transient spectrometer capable of multichannel shot-to-shot detection at 90 kHz. Importantly, we find that several high-speed cameras exhibit a time-domain fixed pattern noise resulting from interleaved analog-to-digital converters that is particularly detrimental to the conventional "ON/OFF" modulation scheme used in pump-probe spectroscopy. Using a modified modulation and data processing scheme, we achieve a noise level of $10^{-5}$ OD for an integration time of four seconds, an order of magnitude lower than for commercial 1 kHz transient spectrometers. We leverage the high sensitivity of this system to measure the differential transmission of monolayer graphene at low pump fluence. We show that signals on the order of $10^{-6}$ OD can be measured, enabling a new data acquisition regime for low dimensional materials

A systematic review of biological changes in surgeons’ acute stress levels during surgery

Background: While a degree of stress facilitates learning and task performance, excessive stress in surgeons may lead to poor patient outcomes, with maladaptive stress as a risk factor for surgeon burnout or self-harm through mechanisms including substance abuse, and suicide. We aim to systematically review publications investigating how measures of surgeons’ acute biological stress change during surgery. Methods: Medline, Embase, Cochrane library, and The United States, Australian, and European clinical trials registries were searched using the terms stress; surgeon; cortisol; skin conductance; and heart rate. Studies had to report at least one measure of biological stress related to surgery or simulated surgical exercise and have been published between January 1996 to June 2022. Results: Twenty-eight studies with a total of 433 participants met inclusion criteria with cortisol, heart rate, heart rate variability, and electrodermal activity being reported. Salivary cortisol was measured in four studies with conflicting directional changes reported. Mean heart rate increased in nine studies (by 6-22 beats/minute), however the impact of the physical work of surgery was not reported. Heart rate variability, as measured by low-frequency to high-frequency ratio, was significantly increased in three of six studies. One study measured electrodermal activity reporting significant increase in skin conductance in a simulation setting. Conclusion: While some biological measures appear able to detect changes in acute stress in surgeons (particularly heart rate), appropriate measures of stress during non-stressful and stressful surgery are yet to be fully identified. Importantly, there are no current pathways for identifying surgeons at risk of burnout or self-harm and this is a critical unmet research need

Understanding And Confronting Alcohol-Induced Risky Behavior Among College Students

Confronting alcohol abuse is a challenge for most higher education institutions.  Each year, students are admitted to hospitals for issues arising from the misuse of alcohol.  The deaths of some engaged in alcohol related activities is especially worrisome.  Factors such as age and financial standing could impact the likelihood of abuse.  So-called drinking “games” have potentially altered student perceptions of alcohol consumption and may lead to reckless behavior.  This study looks at perceptions of alcohol use among college students and investigates the level of support a late night shuttle system might garner if offered to students on a college campus. &nbsp

Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses

Infectious organisms and damage of cells can activate inflammasomes, which mediate tissue inflammation and adaptive immunity. These mechanisms evolved to curb the spread of microbes and to induce repair of the damaged tissue. Chronic activation of inflammasomes, however, contributes to non-resolving inflammatory responses that lead to immuno-pathologies. Inflammasome-activated cells undergo an inflammatory cell death associated with the release of potent pro-inflammatory cytokines and poorly characterized extracellular vesicles (EVs). Since inflammasome-induced EVs could signal inflammasome pathway activation in patients with chronic inflammation and modulate bystander cell activation, we performed a systems analysis of the ribonucleic acid (RNA) content and function of two EV classes. We show that EVs released from inflammasome-activated macrophages carry a specific RNA signature and contain interferon beta (IFNbeta). EV-associated IFNbeta induces an interferon signature in bystander cells and results in dampening of NLRP3 inflammasome responses. EVs could, therefore, serve as biomarkers for inflammasome activation and act to prevent systemic hyper-inflammatory states by restricting NLRP3 activation in bystander cells

An Investigation Into Alternative Television Viewership Habits Of College Students

Television viewership through the use of digital video recorders (DVRs) and the Internet are affecting viewership statistics. The utilization of the Internet by students to view television programs mandates that future marketing efforts be directed more toward the Internet instead of traditional television advertisements.  Research focused on the television viewing habits of college students, current challenges in television advertising and marketing and the increasing use of DVRs and the Internet are investigated

OUTCOMES FROM OUR VISITING TEACHING FELLOW PROGRAM IN THE SCHOOL OF PHYSICS

In 2017 a visiting teaching fellow program was introduced in the School of Physics, University of New South Wales. Each year a high school teacher is seconded to the university to teach first year classes and develop outreach materials. This has led to a very fruitful partnership between teachers and academics. Projects that the teaching fellows have worked on include the introduction of online depth study resources to support the introduction of new Higher School Certificate syllabi; the opening of the first year physics laboratory out of term for school excursions; and the introduction of a summer school program, SciX, to support the extension science syllabus. Many of these projects expanded from physics to encompass the entire science faculty. The teachers have found the experience rewarding and refreshing while academics have benefitted from having a high school teacher’s insights into the background of our incoming students

Support needs and experiences of young people living in families with mental illness

Introduction: Children and adolescents living in families affected by mental illness are at elevated risk of developing mental health problems. A range of interventions have been designed to help these young people; however, the effectiveness of these programs is, in some cases, mixed. Our aim was to understand in detail the support needs and experiences of a group of Australian children and adolescents living in families with mental illness. Methods: Our study is a qualitative in nature. In 2020−2021, we interviewed 25 Australian young people (Mage = 13.60, SD = 2.26, 20 females and 5 males) living with family members affected by mental illness to understand their (the young people's) experiences, and to identify the types of support that these young people considered important or effective. We conducted reflexive thematic analyses of interview data, underpinned by interpretivist assumptions. Results: We identified seven themes within two higher-order categories reflecting our aims to understand (1) lived experiences within families affected by mental illness (i.e., increased responsibilities, missing out, and stigmatization), and (2) support experiences, needs, and preferences (i.e., respite, shared experiences with like-minded others, education, and flexibility). Conclusions: Our findings hold substantial practical value by informing services, interventions, and conversations that better support young people living in families affected by mental illness