The cyber simulation terrain: Towards an open source cyber effects simulation ontology

Cyber resilience is characterised by an ability to understand and adapt to changing network conditions, including cyber attacks. Cyber resilience may be characterised by an effects-based approach to missions or processes. One of the fundamental preconditions underpinning cyber resilience is an accurate representation of current network and machine states and what missions they are supporting. This research outlines the need for an ontological network representation, drawing on existing literature and implementations in the domain. This work then introduces an open-source ontological representation for modelling cyber assets for the purposes of Computer Network Defence. This representation encompasses computers, network connectivity, users, software, vulnerabilities and exploits and aims for interoperability with related representations in common use. The utility of this work is highlighted against a functional use-case depicting a realistic operational network and mission. Finally, a future research direction is defined

Drawing From SEFI Ethics Knowledge To Support Eco-Ethics Education Within The European University Of Technology

We are leading a project called Ethico within the European University of Technology (EUt). Ethico aims to design and promote the uptake of innovative, ecological ethics for technological education. This practice paper briefly summarizes the aims and structure of the Ethico project, and then focuses on the work completed as part of the teacher training module developed in Cluj, 7-9th March, 2023. This workshop drew its conceptual framework from the short abstracts currently available for the Engineering Ethics Education Handbook. The structure developed was then implemented in a student facing workshop in Troyes between the 10-14th July 2023. The handbook is under development by SEFI’s Ethics special interest group, who shared the content with us (the second author of this paper is part of both projects). We drew particularly from Theme 3 of the handbook, which covers Teaching Methods for Engineering Ethics Education (EEE), for the Intensive Study Periods in Cluj and Troyes. Drawing from these EEE abstracts, we designed and tested a teacher training course, with the express aim of achieving flexibility for appropriate application in diverse cultural and administrative university settings. This is because the EUt is comprised of eight universities in eight separate European countries. We explored how we could apply the literature review chapter of theme 3 (on education methods) and of the EEE Handbook, as well as the dialogical/reflective chapter, and some of the specific pedagogical methods for building student awareness, understanding and analytical decision making in ethics. Our work in Cluj focused on three of the Student-Centred Learning approaches presented in the Handbook— case studies, challenge- and problem-based learning, and Virtuous Practice Design—with very promising results. The paper examines the ethical model engaged with and the teaching models developed at the EUt event in Cluj and Troyes using the EEE Handbook. It outlines our proposed module for eco-ethics in technological education, highlighting the key tensions for implementation in cross-cultural and interdisciplinary contexts and incorporates preliminary feedback from student participants

Feedback from activity trackers improves daily step count after knee and hip arthroplasty: A randomized controlled trial

Background: Commercial wrist-worn activity monitors have the potential to accurately assess activity levels and are being increasingly adopted in the general population. The aim of this study was to determine if feedback from a commercial activity monitor improves activity levels over the first 6 weeks after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: One hundred sixty-three consecutive subjects undergoing primary TKA or THAwere randomized into 2 groups. Subjects received an activity tracker with the step display obscured 2 weeks before surgery and completed patient-reported outcome measures (PROMs). On day 1 after surgery, participants were randomized to either the “feedback (FB) group” or the “no feedback (NFB) group.” The FB group was able to view their daily step count and was given a daily step goal. Participants in the NFB group wore the device with the display obscured for 2 weeks after surgery, after which time they were also able to see their daily step count but did not receive a formal step goal. The mean daily steps at 1, 2, 6 weeks, and 6 months were monitored. At 6 months after surgery, subjects repeated PROMs and daily step count collection. Results: Of the 163 subjects, 95 underwent THA and 68 underwent TKA. FB subjects had a significantly higher (P \u3c .03) mean daily step count by 43% in week 1, 33% in week 2, 21% in week 6, and 17% at 6 months, compared with NFB. The FB subjects were 1.7 times more likely to achieve a mean 7000 steps per day than the NFB subjects at 6 weeks after surgery (P ¼ .02). There was no significant difference between the groups in PROMs at 6 months. Ninety percent of FB and 83% of NFB participants reported that they were satisfied with the results of the surgery (P ¼ .08). At 6 months after surgery, 70% of subjects had a greater mean daily step count compared with their preoperative level. Conclusion: Subjects who received feedback from a commercial activity tracker with a daily step goal had significantly higher activity levels after hip and knee arthroplasty over 6 weeks and 6 months, compared with subjects who did not receive feedback in a randomized controlled trial. Commercial activity trackers may be a useful and effective adjunct after arthroplasty

Microfluidic-based Bacterial Molecular Computing on a Chip

Biocomputing systems based on engineered bacteria can lead to novel tools for environmental monitoring and detection of metabolic diseases. In this paper, we propose a Bacterial Molecular Computing on a Chip (BMCoC) using microfluidic and electrochemical sensing technologies. The computing can be flexibly integrated into the chip, but we focus on engineered bacterial AND Boolean logic gate and ON-OFF switch sensors that produces secondary signals to change the pH and dissolved oxygen concentrations. We present a prototype with experimental results that shows the electrochemical sensors can detect small pH and dissolved oxygen concentration changes created by the engineered bacterial populations’ molecular signals. Additionally, we present a theoretical model analysis of the BMCoC computation reliability when subjected to unwanted effects, i.e., molecular signal delays and noise, and electrochemical sensors threshold settings that are based on either standard or blind detectors. Our numerical analysis found that the variations in the production delay and the molecular output signal concentration can impact on the computation reliability for the AND logic gate and ON-OFF switch. The molecular communications of synthetic engineered cells for logic gates integrated with sensing systems can lead to a new breed of biochips that can be used for numerous diagnostic applications

Novel Role of Hypoxia in Ovarian Cancer Chemo Resistance through Epigenetic Regulation of HIF1α

Ovarian cancer is the fifth deadliest cancer in woman, and epithelial malignancies account for 90% of cases. Tumor recurrence after chemotherapy or radiation remains a major obstacle to successful ovarian cancer treatment. Despite the large number of studies, molecular events that govern the emergence of aggressive therapy-resistant cells after chemotherapy are poorly defined. Genetic modifications, such as copy number variation (CNV), play an important role in controlling the expression of genes that are involved in chemo resistance. We analyzed CNV data that is publically available through the Cancer Genome Atlas and others. Of particular interest was the transcription factor HIF1α which plays an integral role in oxidative stress response such as those induced by chemotherapy reagents? The present study provides evidence for the rare escape of tumor cells from drug-induced cell death by entering a non-cycling senescent state. We report the adaptive response of human ovarian surface epithelium cells to CoCl2, a chemical hypoxia-mimicking agent resulting in a senescent-like state of chemo resistant cells. The effect of the treatment was evaluated on CNV of HIF-1α gene expression, cell proliferation, survival, and tumor invasiveness

Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy

Background: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. Methods: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses. Results: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy. Conclusions: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy

Utility of preoperative blood screening before hip and knee arthroplasty

Background: It is engrained in medical training that routine blood screening prior to arthroplasty is necessary for optimal patient care. There is little evidence to support their utility and the aggregate cost to the health system. The purpose of this study was to evaluate preoperative blood screening by identifying the frequency of an abnormal result and to examine the influence of age, gender and body mass index on the frequency of abnormal blood pathology. Methods: This is a retrospective review of 1000 patients from a single centre who underwent elective primary hip or knee arthroplasty from 2015 to 2017. Abnormal blood results were identified and clinically relevant intervals were created for routine markers. Results: A total of 939 patients had available pathology results with 84% identified as having an abnormal result and 47% having a clinically important range. Abnormal liver function tests and ferritin were most common. With increasing age, there was a significant increase in rates of abnormal clinically important range, renal dysfunction, abnormal haemoglobin and erythrocyte sedimentation rate. Males and patients with body mass index \u3e40 had an increased rate of abnormal results, particularly liver function tests. Conclusion: The ordering of preoperative investigations prior to lower limb arthroplasty is recommended by the National Institute for Health and Care Excellence guidelines, alleviating concern of post-operative complications and covering medicolegal issues. Our study determined a high frequency of abnormal results, justifying routine blood screening is recommended prior to surgery, particularly for the elderly, males and obese patients

Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report

Newborn screening for cystic fibrosis offers the opportunity for early intervention and improved outcomes. This summary, resulting from a workshop sponsored by the Cystic Fibrosis Foundation to facilitate implementation of widespread high quality cystic fibrosis newborn screening, outlines the steps necessary for success based on the experience of existing programs. Planning should begin with a workgroup composed of those who will be responsible for the success of the local program, typically including the state newborn screening program director and cystic fibrosis care center directors. The workgroup must develop a screening algorithm based on program resources and goals including mechanisms available for sample collection, regional demographics, the spectrum of cystic fibrosis disease to be detected, and acceptable failure rates of the screen. The workgroup must also ensure that all necessary guidelines and resources for screening, diagnosis, and care be in place prior to cystic fibrosis newborn screening implementation. These include educational materials for parents and primary care providers; systems for screening and for providing diagnostic testing and counseling for screen-positive infants and their families; and protocols for care of this unique population. This summary explores the benefits and risks of various screening algorithms, including complex situations that can occur involving unclear diagnostic results, and provides guidelines and sample materials for state newborn screening programs to develop and implement high quality screening for cystic fibrosis

Global Carbon Budget 2022

Accurate assessment of anthropogenic carbon dioxide (CO$_2$) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodologies to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO$_2$ emissions (E$_{FOS}$) are based on energy statistics and cement production data, while emissions from land-use change (E$_{LUC}$), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO$_2$ concentration is measured directly, and its growth rate (G$_{ATM}$) is computed from the annual changes in concentration. The ocean CO$_2$ sink (S$_{OCEAN}$) is estimated with global ocean biogeochemistry models and observation-based data products. The terrestrial CO$_2$ sink (S$_{LAND}$) is estimated with dynamic global vegetation models. The resulting carbon budget imbalance (B$_{IM}$), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2021, E$_{FOS}$ increased by 5.1 % relative to 2020, with fossil emissions at 10.1 ± 0.5 GtC yr$^{−1}$ (9.9 ± 0.5 GtC yr$^{−1}$ when the cement carbonation sink is included), and E$_{LUC}$ was 1.1 ± 0.7 GtC yr$^{−1}$, for a total anthropogenic CO$_2$ emission (including the cement carbonation sink) of 10.9 ± 0.8 GtC yr$^{−1}$ (40.0 ± 2.9 GtCO$_2$). Also, for 2021, G$_{ATM}$ was 5.2 ± 0.2 GtC yr$^{−1}$ (2.5 ± 0.1 ppm yr$^{−1}$), S$_{OCEAN}$ was 2.9  ± 0.4 GtC yr$^{−1}$, and S$_{LAND}$ was 3.5 ± 0.9 GtC yr$^{−1}$, with a B$_{IM}$ of −0.6 GtC yr$^{−1}$ (i.e. the total estimated sources were too low or sinks were too high). The global atmospheric CO$_2$ concentration averaged over 2021 reached 414.71 ± 0.1 ppm. Preliminary data for 2022 suggest an increase in E$_{FOS}$ relative to 2021 of +1.0 % (0.1 % to 1.9 %) globally and atmospheric CO$_2$ concentration reaching 417.2 ppm, more than 50 % above pre-industrial levels (around 278 ppm). Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2021, but discrepancies of up to 1 GtC yr$^{−1}$ persist for the representation of annual to semi-decadal variability in CO$_2$ fluxes. Comparison of estimates from multiple approaches and observations shows (1) a persistent large uncertainty in the estimate of land-use change emissions, (2) a low agreement between the different methods on the magnitude of the land CO$_2$ flux in the northern extratropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set. The data presented in this work are available at https://doi.org/10.18160/GCP-2022 (Friedlingstein et al., 2022b)