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A common network security approach is to create a De‐Militarized Zone (DMZ) comprising two layers of network defense. The DMZ structure provides an extra layer of security between the sensitive information in a network (e.g., research and development files) and the component of the network that must interface with the general internet (e.g., the mail server). We consider a cyber‐attack on a DMZ network where both attacker and defender have limited resources and capabilities to attack and defend, respectively. We study two optimization problems and one game‐theoretic problem. Given that the attacker (defender) knows the potential capabilities of the defender (attacker) in the two layers, we obtain the optimal allocation of resources for the attacker (defender). The two‐optimization problems are not symmetrical. Absent any knowledge regarding the allocation of the adversary's resources, we solve a game‐theoretic problem and obtain some operational insights regarding the effect of combat (e.g., cyber) capabilities and their optimal allocation. [ABSTRACT FROM AUTHOR]

Multiple choice questions (MCQs) are a common form of assessment in medical schools and students seek opportunities to engage with formative assessment that reflects their summative exams. Formative assessment with feedback and active learning strategies improve student learning outcomes, but a challenge for educators, particularly those with large class sizes, is how to provide students with such opportunities without overburdening faculty. To address this, we enrolled medical students in the online learning platform PeerWise, which enables students to author and answer MCQs, rate the quality of other students’ contributions as well as discuss content. A quasi‐experimental mixed methods research design was used to explore PeerWise use and its impact on the learning experience and exam results of fourth year medical students who were studying courses in clinical sciences and pharmacology. Most students chose to engage with PeerWise following its introduction as a noncompulsory learning opportunity. While students perceived benefits in authoring and peer discussion, students engaged most highly with answering questions, noting that this helped them identify gaps in knowledge, test their learning and improve exam technique. Detailed analysis of the 2015 cohort (n = 444) with hierarchical regression models revealed a significant positive predictive relationship between answering PeerWise questions and exam results, even after controlling for previous academic performance, which was further confirmed with a follow‐up multi‐year analysis (2015–2018, n = 1693). These 4 years of quantitative data corroborated students’ belief in the benefit of answering peer‐authored questions for learning.PeerWise use improves academic performance. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are multilineage adult stem cells with considerable potential for cell‐based regenerative therapies. In vitro expansion changes their epigenetic and cellular properties, with a poorly understood impact on DNA damage response (DDR) and genome stability. We report here results of a transcriptome‐based pathway analysis of in vitro‐expanded human bone marrow‐derived mesenchymal stem cell (hBM‐MSCs), supplemented with cellular assays focusing on DNA double‐strand break (DSB) repair. Gene pathways affected by in vitro aging were mapped using gene ontology, KEGG, and GSEA, and were found to involve DNA repair, homologous recombination (HR), cell cycle control, and chromosomal replication. Assays for the recognition (γ‐H2AX + 53BP1 foci) and repair (pBRCA1 + γ‐H2AX foci) of X‐ray‐induced DNA DSBs in hBM‐MSCs show that over a period of 8 weeks of in vitro aging (i.e., about 10 doubling times), cells exhibit a reduced DDR and a higher fraction of residual DNA damage. Furthermore, a distinct subpopulation of cells with impaired DNA DSB recognition was observed. Several genes that participate in DNA repair by HR (e.g., Rad51, Rad54, BRCA1) show a 2.3‐ to fourfold reduction of their mRNA expression by qRT‐PCR. We conclude that the in vitro expansion of hMSCs can lead to aging‐related impairment of the recognition and repair of DNA breaks. [ABSTRACT FROM AUTHOR]

Radiation exposure can evoke cellular stress responses. Emerging recognition that long non‐coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A‐ antisense radiation‐induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri‐methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S‐adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer‐related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.Methods: We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans-theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intent-to-treat analyses using generalized estimating equations for the binary outcome.Results: Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).Conclusion: Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA-related autoantibody production or RA development. [ABSTRACT FROM AUTHOR]

Firing multiple artillery rounds from the same location has two main benefits: a high rate of fire at the enemy and improved accuracy as the shooter's aim adjusts to previous rounds. However, firing repeatedly from the same location carries significant risk that the enemy will detect the artillery's location. Therefore, the shooter may periodically move locations to avoid counter‐battery fire. This maneuver is known as the shoot‐and‐scoot tactic. This article analyzes the shoot‐and‐scoot tactic for a time‐critical mission using Markov models. We compute optimal move policies and develop heuristics for more complex and realistic settings. Spending a reasonable amount of time firing multiple shots from the same location is often preferable to moving immediately after firing an initial salvo. Moving frequently reduces risk to the artillery, but also limits the artillery's ability to inflict damage on the enemy. [ABSTRACT FROM AUTHOR]

Since the mid‐1990s, most Canadian provinces have enacted balanced budget laws (BBLs). Critics argue that these laws are empty political gestures that are ignored during economic slowdowns. We consider BBLs in the Canadian provinces from 1981 to 2013 and find that provinces with stronger rules had better deficit and debt records overall. Recessions make it more difficult to achieve positive outcomes, but we find no obvious difference between the effects of BBLs during normal economic conditions and “bad times.” We conclude with suggestions for how the design of BBLs could take better account of jurisdiction‐specific business cycles. [ABSTRACT FROM AUTHOR]

We analyze an interdiction scenario where an interceptor attempts to catch an intruder as the intruder moves through the area of interest. A motivating example is the detection and interdiction of drug smuggling vessels in the Eastern Pacific and Caribbean. We study two models in this article. The first considers a nonstrategic target that moves through the area without taking evasive action to avoid the interdictor. We determine the optimal location the interceptor should position itself to best respond when a target arrives. The second model analyzes the strategic interaction between the interceptor and intruder using a Blotto approach. The intruder chooses a route to travel on and the interceptor chooses a route to patrol. We model the interaction as a two-player game with a bilinear payoff function. We compute the optimal strategy for both players and examine several extensions. © 2017 Wiley Periodicals, Inc. Naval Research Logistics, 64: 29-40, 2017 [ABSTRACT FROM AUTHOR]

Most Canadian provinces have introduced legislation to require politicians of all ideological stripes to meet annual balanced budget (BB) targets. Critics of this type of legislation argue that it is unnecessary, confining, and subject to manipulation. We examine provincial balanced budget legislation before and after the Great Recession and argue that the response of provinces needs to be evaluated taking into account the multiple objectives of fiscal policy and the behavioural changes that the rules introduce, including creative non-compliance. Rules should be evaluated on their ability to contribute to good fiscal governance rather than on their stringency. [ABSTRACT FROM AUTHOR]

While each election provides the Canadian House of Commons with a fresh batch of politicians, no consideration has been given to the question of whether the quality of politicians is improving. Yet improving quality has been the focus of several commissions urging increases in MP compensation. This article addresses the competence and compensation questions by asking whether changes in levels of compensation might make a difference to the educational qualifications of political leaders. We assemble a unique dataset of 1,291 federal politicians elected to the Canadian House of Commons from 1993 to 2011 and show that prime ministers do have a preference for more highly educated MPs when filling ministerial and other executive positions. Our findings suggest that certain subgroups of MPs, particularly educated women, may be attracted by upward shifts in compensation. We discuss the reasons for these effects and the relative importance of compensation in career decisions. [ABSTRACT FROM AUTHOR]

A 3D microtissues using T47D and JIMT-1 cells were generated to analyze tissue-like response of breast cancer cells after combined human epidermal growth factor receptor 2 ( HER2)-targeted treatment and radiation. Following lentiviral knockdown of HER2, we compared growth rate alterations using 2D monolayers, 3D microtissues, and mouse xenografts. Additionally, to model combined therapeutic strategies, we treated HER2-depleted T47D cells and 3D microtissues using trastuzumab (anti- HER2 antibody) in combination with irradiation. Comparison of HER2 knockdown with corresponding controls revealed growth impairment due to HER2 knockdown in T47D 2D monolayers, 3D microtissues, and xenografts (after 2, 12, and ≥40 days, respectively). In contrast, HER2 knockdown was less effective in inhibiting growth of trastuzumab-resistant JIMT-1 cells in vitro and in vivo. Combined administration of trastuzumab and radiation treatment was also analyzed using T47D 3D microtissues. Administration of both, radiation (5 Gy) and trastuzumab, significantly enhanced the growth inhibiting effect in 3D microtissues. To improve the predictive power of potential drugs-as single agents or in combination-here, we show that regarding tumor growth analyses, 3D microtissues are highly comparable to outcomes derived from xenografts. Considering increased limitations for animal experiments on the one hand and strong need of novel drugs on the other hand, it is indispensable to include highly reproducible 3D microtissue platform in preclinical analyses to validate more accurately the capacity of future drug-combined radiotherapy. [ABSTRACT FROM AUTHOR]

Consider a patrol problem, where a patroller traverses a graph through edges to detect potential attacks at nodes. An attack takes a random amount of time to complete. The patroller takes one time unit to move to and inspect an adjacent node, and will detect an ongoing attack with some probability. If an attack completes before it is detected, a cost is incurred. The attack time distribution, the cost due to a successful attack, and the detection probability all depend on the attack node. The patroller seeks a patrol policy that minimizes the expected cost incurred when, and if, an attack eventually happens. We consider two cases. A random attacker chooses where to attack according to predetermined probabilities, while a strategic attacker chooses where to attack to incur the maximal expected cost. In each case, computing the optimal solution, although possible, quickly becomes intractable for problems of practical sizes. Our main contribution is to develop efficient index policies-based on Lagrangian relaxation methodology, and also on approximate dynamic programming-which typically achieve within 1% of optimality with computation time orders of magnitude less than what is required to compute the optimal policy for problems of practical sizes. © 2014 Wiley Periodicals, Inc. Naval Research Logistics, 61: 557-576, 2014 [ABSTRACT FROM AUTHOR]

In Canada, pay-for-performance ( PFP) systems to compensate senior public servants have been established in several jurisdictions despite arguments by academics who doubt their efficacy in public sector environments characterized by high levels of intrinsic motivation. This article traces the pattern of PFP in Canada and distinguishes among 'aggressive,' 'passive,' and 'reluctant' regimes. It explores why PFP is growing in popularity despite its acknowledged limitations. We canvass three theoretical perspectives and review evidence from interviews with key officials in a number of jurisdictions. The article contributes to our knowledge of managerial innovations by revealing the variety of motivations behind PFP. [ABSTRACT FROM AUTHOR]

Background Although lentiviral transduction methods are widely used, their broader application is dependent upon the optimization of lentiviral transduction efficiency for a broad range of cell types. In the present study, we focus on the evaluation of two chemical classes with respect to their ability to increase lentiviral transduction without cytotoxicity. Methods We compared the activity of adjuvants that are already used for lentivirus delivery with that of novel adjuvants selected on the basis of their chemical and physical characteristics. Results The novel poloxamer synperonic F108 demonstrated superior characteristics for enhancing lentiviral transduction over the best-in-class polybrene-assisted transduction. The results revealed that poloxamer synperonic F108 exhibited the dual benefits of low toxicity and a high efficiency of lentiviral gene delivery into a range of different primary cell cultures. In the presence of poloxamer synperonic F108, cells showed an increased propidium dye influx indicating a re-organization of membrane microstructures accompanying lentivirus uptake. The administration of a mixture of poloxamer synperonic F108 with polybrene further enhanced lentiviral transduction rates. Conclusions The results obtained in the present study indicate that a contribution to efficiency is made by each adjuvant, with polybrene acting as a charge protector and poloxamer synperonic F108 as a membrane modulator. Therefore, poloxamer synperonic F108, either alone or in combination, can lead to the optimization of large-scale lentiviral transduction approaches. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent studies show that transfusing older blood may lead to increased mortality. This raises the issue of whether transfusing fresher blood can be achieved without jeopardizing blood availability. STUDY DESIGN AND METHODS: We propose a simple family of policies that is defined by a single threshold: rather than transfusing the oldest available blood that is younger than 42 days, we transfuse the oldest blood that is younger than the threshold, and if there is no blood younger than the threshold then we transfuse the youngest blood that is older than the threshold. To assess this policy, we build a simulation model using data from Stanford University Medical Center. We focus on the tradeoff between the mean age of transfused blood and the fraction of transfused blood that is imported. RESULTS: For hospitals in which the local supply is greater than demand, our policy with a threshold of 14 days leads to a decrease of 10 to 20 days in the mean age of transfused blood while increasing the fraction of imported blood to less than 0.005 (i.e., 0.5%). If the health benefits from transfusing fresher blood can be confirmed by randomized clinical trials, then conservative assumptions suggest that this policy could reduce the annual number of transfused patients who die within 1 year by 20,000. CONCLUSION: The proposed allocation policy with a threshold of 14 days could allow many US hospitals to significantly reduce the age of transfused blood, thereby possibly reducing morbidity and mortality, while having a negligible impact on supply chain operations. [ABSTRACT FROM AUTHOR]

We construct a mathematical model of aerosol (i.e., droplet-nuclei) transmission of influenza within a household containing one infected and embed it into an epidemic households model in which infecteds occasionally infect someone from another household; in a companion paper, we argue that the contribution from contact transmission is trivial for influenza and the contribution from droplet transmission is likely to be small. Our model predicts that the key infection control measure is the use of N95 respirators, and that the combination of respirators, humidifiers, and ventilation reduces the threshold parameter (which dictates whether or not an epidemic breaks out) by ≈20% if 70% of households comply, and by ≈40% if 70% of households and workplaces comply (≈28% reduction would have been required to control the 1918 pandemic). However, only ≈30% of the benefits in the household are achieved if these interventions are used only after the infected develops symptoms. It is also important for people to sleep in separate bedrooms throughout the pandemic, space permitting. Surgical masks with a device (e.g., nylon hosiery) to reduce face-seal leakage are a reasonable alternative to N95 respirators if the latter are in short supply. [ABSTRACT FROM AUTHOR]

We formulate and analyze an optimal stopping problem concerning a terrorist who is attempting to drive a nuclear or radiological weapon toward a target in a city center. In our model, the terrorist needs to travel through a two-dimensional lattice containing imperfect radiation sensors at some of the nodes, and decides at each node whether to detonate the bomb or proceed. We consider five different scenarios containing various informational structures and two different sensor array topologies: the sensors are placed randomly or they form an outer wall around the periphery of the city. We find that sensors can act as a deterrent in some cases, and that the government prefers the outer wall topology unless the sensors have a very low detection probability and the budget is tight (so that they are sparsely deployed). [ABSTRACT FROM AUTHOR]

In recent years the study of the Canadian Parliament has lost some of its original momentum. Major gaps in research have begun to appear, and critics have argued that students of Parliament take a much too docile, uncritical view of parliamentary government as it is practiced in Canada. This article reviews recent research on the Canadian Parliament in light of these criticisms and compares it to more established work on the subject. The prospects are not as bleak as the critics maintain, but the authors express concern that Parliament may no longer pose the kind of intellectual challenge that attracted researchers in previous generations. [ABSTRACT FROM AUTHOR]

Although conflict of interest is a problem endemic to representative institutions, it manifests itself in different ways from one system to the next. This paper examines how conflict of interest has been interpreted and managed in the United States Congress and in the British House of Commons. Differences in the regulatory systems are described, and the argument is made that the crucial distinction is the greater autonomy members of Parliament have in interpreting and resolving conflicts of interest. This autonomy (or the lack of it) arises, we suggest, out of fundamental institutional arrangements, specifically the theory of representation employed in each system and the degree of institutional autonomy enjoyed by each legislative body. [ABSTRACT FROM AUTHOR]

This article examines the policy interests of backbenchers in the Ontario and Nova Scotia legislatures and tests the hypothesis that the manner in which interests are defined is dependent upon the nature of political ambition. In both provinces those members who aspire to cabinet positions are more inclined than others to define their interests in broad terms and to omit any discussion of their constituency in describing their interests. These relationships are sustained in the presence of control variables. The conclusions of this paper bear on the issue of parochialism in provincial politics and the problem of generating and sustaining challenges to political executives. [ABSTRACT FROM AUTHOR]