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We evaluate an adaptive optimisation methodology, Bayesian optimisation (BO), for designing a minimum weight explosive reactive armour (ERA) for protection against a surrogate medium calibre kinetic energy (KE) long rod projectile and surrogate shaped charge (SC) warhead. We perform the optimisation using a conventional BO methodology and compare it with a conventional trial-and-error approach from a human expert. A third approach, utilising a novel human-machine teaming framework for BO is also evaluated. Data for the optimisation is generated using numerical simulations that are demonstrated to provide reasonable qualitative agreement with reference experiments. The human-machine teaming methodology is shown to identify the optimum ERA design in the fewest number of evaluations, outperforming both the stand-alone human and stand-alone BO methodologies. From a design space of almost 1800 configurations the human-machine teaming approach identifies the minimum weight ERA design in 10 samples.

Abstract Recently, the number of online courses provided for university students around the world has increased substantially. Instruction is delivered most commonly through either asynchronous video lectures (pre-recorded videos with no real-time communication) or synchronous video lectures (live-streamed videos with real-time communication). From a learning perspective, it is important to capture the interest of learners based on specific situational aspects of both asynchronous and synchronous video lectures, and situational interest of learners may vary depending on the overall intrinsic qualities of each modality. Additionally, there may be variations in regards to the way in which self-efficacy interacts with situational interest depending on which modality is used. This study examines survey responses of university students (n = 93) in South Korea to determine if students perceive differences in situational interest between two different conditions: asynchronous video lectures and synchronous video lectures. Additionally, the difference between situational interest levels of learners with low self-efficacy and learners with high self-efficacy within each condition was examined. The main results showed no overall difference in situational interest between the two conditions and no difference in situational interest between learners with low self-efficacy and learners with high self-efficacy in the synchronous video lecture condition. However, there was a significant difference in situational interest found between learners with low self-efficacy and learners with high self-efficacy in the asynchronous video lecture condition. Results are explained through the differing effects of self-efficacy on situational interest based on the amount of autonomy provided in online learning environments.

Learner control allows for greater autonomy and is supposed to benefit learning motivation, but it might be more advantageous for students with specific learner characteristics. The current study looks into the relationships between self-regulated learning, cognitive load, and performance within learner-controlled environments. The research was conducted in an asynchronous online setting, allowing for learner control. Cognitive load and self-regulated learning were measured using self-report questionnaires. Performance was assessed through case solutions. The participants were 97 graduate law students studying the civil code. Analysis based on structural equation modeling showed that both prior knowledge and self-regulated learning skills significantly contribute to the increase in germane cognitive load and are positively correlated with performance. The implications of these findings underscore the critical role of prior knowledge and self-regulated learning skills in shaping the cognitive processes involved in learning, ultimately impacting academic achievement. These results emphasize the need for careful consideration of learner-control options in asynchronous online environments.

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

Abstract The use of media within online university courses has been shown to aid the learning process with the delivery of information through various formats. However, issues that inhibit learning have been found when media are used inappropriately. Based on an examination of extant media research, this study arranges common media delivery problems into five main categories: pace, intelligibility, quality, media diversity, and congruence. Students taking online courses were asked to comment on the media used in their classes. Each of their comments was paired with one of the five categories with justification provided for the categorizations. Through analysis of these learner comments, this study examines the extent to which media delivery problems occur among a specific sample of online university learners in South Korea. The underlying pedagogy that explains the issues caused by inadequate delivery of media is also discussed, followed by recommended solutions that can address such pedagogical concerns. The results not only highlight existing solutions to these types of media problems but also build on them by suggesting other techniques in which media can be delivered so that the overall online learning experience may be enhanced.

The use of worked examples has been shown to be an effective instructional method for reducing cognitive load and successfully engaging in problem-solving. Extant research often views worked examples as an integrated part of direct instruction. Studies have examined the problem-solving effects of worked examples used in tandem with instructional explanations. However, a gap exists in research focusing on the individual problem-solving effects of example-free instructional explanations and worked examples containing no instructional explanation. This study uses a method in which worked examples are separated from direct instruction to examine the problem-solving effects of individual parts of such instruction, namely example-free instruction and worked examples containing no instructional explanation. Considering the importance of critical thinking skills in the current educational environment, the current study was conducted on a group of university students (n = 32) studying critical thinking in South Korea. Results showed that example-free instruction was more effective for problem-solving than worked examples containing no instructional explanation. Additionally, participants reported more efficient cognitive processing ability when critical thinking problems were presented through instructional explanation rather than worked examples. These results allow for a granular look at the different aspects of direct instruction and their effects on cognitive load and problem-solving.

There has been a call in recent years for an integration of cognitive load theory into instructed second language acquisition practices to assist language learners by taking advantage of theories on human cognitive architecture. This paper seeks to move the conversation on how this integration might be achieved by presenting findings from survey data conducted with learners enrolled online courses at a cyber-university in South Korea (n = 68). Findings show a statistically significant positive relationship between distraction and extraneous load. These results are used to postulate a model for explaining the how the effects of extraneous load on attention can be integrated into second language learning theory. Pedagogic implications of this are the value of explicitly signaling key vocabulary and grammar, ensure spatial and temporal considerations are made when using multimodal instruction, and placing learners at the center of decisions on the blend of media they experience in instruction.

High-performance computing (HPC) enables both academia and industry to accelerate simulation-driven product development processes by providing a massively parallel computing infrastructure. In particular, the automation of high-fidelity computational fluid dynamics (CFD) analyses aided by HPC systems can be beneficial since computing time decreases while the number of significant design iterations increases. However, no studies have quantified these effects from a product development point of view yet. This article evaluates the impact of HPC and automation on product development by studying a formula student racing team as a representative example of a small or medium-sized company. Over several seasons, we accompanied the team, and provided HPC infrastructure and methods to automate their CFD simulation processes. By comparing the team’s key performance indicators (KPIs) before and after the HPC implementation, we were able to quantify a significant increase in development efficiency in both qualitative and quantitative aspects. The major aerodynamic KPI increased up to 115%. Simultaneously, the number of expedient design iterations within one season increased by 600% while utilizing HPC. These results prove the substantial benefits of HPC and automation of numerical-intensive simulation processes for product development.

Media diversity within video lectures has been shown to have an effect on students who participate in both flipped classes as well as online courses. While some research claims that content delivered through multiple sources leads to more learning, contrasting research makes the claim that too much media hinders cognitive processing. The present study investigated the effects of varying levels of instructional media delivered to students (n=110) within a flipped scientific writing course to investigate the relationship between higher levels of media diversity and student performance. Results showed that more diversity led to lower levels of performance. It was also found that higher levels of media diversity correlated with higher levels of students’ scanning between different forms of media, possibly contributing to the lower levels of performance. The implications of these results provide insight into the optimal level of media diversity, and on student behavior that can affect learning.

As an alternative to powder-bed based processes, metal parts can be additively manufactured by extrusion based additive manufacturing. In this process, a highly filled polymer filament is deposited and subsequently debindered and sintered. Choosing a proper orientation of the part that satisfies the requirements of the debinding and sintering processes is crucial for a successful manufacturing process. To determine the optimal orientation for debinding, first, the part must be scaled in order to compensate the sinter induced shrinkage. Then, a finite element analysis is performed to verify that the maximum stresses due to the dead load do not exceed the critical stress limits. To ease this selection process, an approach based on open source software is shown in this article to efficiently determine a part’s optimal orientation during debinding. This automates scaling, debinding simulation, and postprocessing for all six main directions. The presented automated simulation framework is examined on three application examples and provides plausible results in a technical context for all example parts, leading to more robust part designs and a reduction of experimental trial and error. Therefore, the presented framework is a useful tool in the product development process for metal extrusion additive manufacturing applications.

Semi-formal learning is used to describe learning that is directed towards the goals of a formal learning institution but outside of the learning structure of a specific class. Students studying online may form semi-formal groups to increase their knowledge of the content by interacting with other learners taking the same class. This study of cyber university students (n = 2042) involved looking at the relationship between semi-formal learning groups and levels of germane load. Furthermore, this study sought to understand what role group work plays in moderating the relationship between motivation and germane load. This study found that highly motivated students had higher levels of germane load, and that group work negatively moderated that relationship. In other words, while all students benefited from group work, students with lower levels of motivation benefited more than students with high levels of motivation. This research fills an important gap by showing the value this type of group work can have for all learners, particularly those who may otherwise struggle.

Online instructors need to avoid unclear and confusing explanations of content, which can reduce the quality of learning. Extraneous load is reflective of poor instruction, in that it directs student effort towards processing information that does not contribute to learning. However, students may be able to manage poor instruction through effort regulation. Students who show high levels of effort have been shown to overcome poor instruction in some cases. This study analyzed survey responses from South Korean university students studying online (n = 1,575) to examine the relationship between self-regulated effort and germane load within varying extraneous load conditions. The experimental design separated extraneous load responses into three conditions (low, medium, high). Within each extraneous load condition, self-regulated effort responses were also separated (low, medium, high). The results showed that as extraneous load increased, self-regulated effort had a weaker relationship with germane load. It was also found that the use of effort regulation is effective only when dealing with low and mid-level extraneous load situations and that use of such strategies within high extraneous load situations was not effective. These results show the importance of improving instruction to reduce extraneous cognitive load, in that, not even high levels of effort can overcome poor quality instruction.

Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels.Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation.We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants.

Quantum processors based on linear arrays of trapped ions have achieved exceptional performance, but scaling to large qubit numbers requires realizing two-dimensional ion arrays as envisioned in the quantum charge-coupled device (QCCD) architecture. Here, we present a scalable method for the control of ion crystals in a grid-based surface-electrode Paul trap and characterize it in the context of transport operations that sort and reorder multispecies crystals. By combining cowiring of control electrodes at translationally symmetric locations in each grid site with the sitewise ability to exchange the voltages applied to two special electrodes gated by a binary input, site-dependent operations can be achieved using only a fixed number of analog voltage signals and a single digital input per site. In two separate experimental systems containing nominally identical grid traps, one using ^{171}Yb^{+}-^{138}Ba^{+} crystals and the other ^{137}Ba^{+}-^{88}Sr^{+}, we demonstrate this method by characterizing the conditional intrasite crystal reorder and the conditional exchange of ions between adjacent sites on the grid. Averaged across a multisite region of interest, we measure subquanta motional excitation in the axial in-phase and out-of-phase modes of the crystals following these operations at exchange rates of 2.5 kHz. In this initial demonstration, the logic controlling the voltage exchange occurs in software, but the applied signals mimic a proposed hardware implementation using crossover switches. These techniques can be further extended to implement other conditional operations in the QCCD architecture such as gates, initialization, and measurement.

How structural segment boundaries modulate earthquake behavior is an important scientific and societal question, especially for the Wasatch fault zone (WFZ) where urban areas lie along multiple fault segments. The extent to which segment boundaries arrest ruptures, host moderate magnitude earthquakes, or transmit ruptures to adjacent fault segments is critical for understanding seismic hazard. To help address this outstanding issue, we conducted a paleoseismic investigation at the Traverse Ridge paleoseismic site (TR site) along the ∼7-km-long Fort Canyon segment boundary, which links the Provo (59 km) and Salt Lake City (40 km) segments of the WFZ. At the TR site, we logged two trenches which were cut across sub-parallel traces of the fault, separated by ∼175 m. Evidence from these exposures leads us to infer that at least 3 to 4 earthquakes have ruptured across the segment boundary in the Holocene. Radiocarbon dating of soil material developed below and above fault scarp colluvial packages and within a filled fissure constrains the age of the events. The most recent event ruptured the southern fault trace between 0.2 and 0.4 ka, the penultimate event ruptured the northern fault trace between 0.6 and 3.4 ka, and two prior events occurred between 1.4 and 6.2 ka (on the southern fault trace) and 7.2 and 8.1 ka (northern fault trace). Colluvial wedge heights of these events ranged from 0.7 to 1.2 m, indicating the segment boundary experiences surface ruptures with more than 1 m of vertical displacement. Given these estimates, we infer that these events were greater than Mw 6.7, with rupture extending across the entire segment boundary and portions of one or both adjacent fault segments. The Holocene recurrence of events at the TR site is lower than the closest paleoseismic sites at the adjacent fault segment endpoints. The contrasts in recurrence rates observed within 15 km of the Fort Canyon fault segment boundary may be explained conceptually by a leaky segment boundary model which permits spillover events, ruptures centered on the segment boundary, and segmented ruptures. The TR site demonstrates the utility of paleoseismology within segment boundaries which, through corroboration of displacement data, can demonstrate rupture connectivity between fault segments and test the validity of rupture models.

Canada’s universal health-care system does not include dental care, which presents problems for both low- and middle-income families. According to the latest Statistics Canada data, out-of-pocket dental expenses are increasing steadily. Lower-income workers struggle with a disproportionate share of these costs, leading one in 4.5 Canadians to avoid visits to the dentist. With dental care becoming increasingly unaffordable and private insurance harder to obtain, it’s time for Canada to consider bringing dental services into the public health system. Policy solutions have tended to fluctuate between a fill-in-the-gaps approach or comprehensive restructuring of dental care. This paper examines two new options: universal first-dollar coverage or denticare, and public dental insurance for all those without it or denticaid. Denticare would cover dental treatment with the same eligibility for public health insurance under the medicare system. Denticaid would only provide this to children under 12 and those lacking private insurance. Both denticare and denticaid would lower overall health-care costs, as improved oral hygiene would reduce rates of chronic and serious diseases. Integrating dentistry into the public health system would lead to increased patient contact, more efficient early screening and referrals. Direct clinical costs are estimated through micro-costing of expected annual dental services used. Indirect administrative costs are estimated through average costing based on existing per-patient administrative costs in the Canadian health-care system. Co-payments for both options are based on five household income brackets with the lowest bracket being exempt and the highest paying the maximum rate. The co-payment for advanced procedures would be 50 per cent and 20 per cent for all other services. Everyone over age 17 would have to pay an annual premium to be enrolled in the public plan; the lowest income brackets would be exempt and the highest would pay the maximum of $400. In denticare, public employees would no longer receive workplace dental benefits on the private market, while those same benefits would make them ineligible for denticaid. National clinical costs for a hypothetical denticare program in 2019, including administrative costs, are estimated at $27.50 billion ($737.09 per capita) with an upper estimate of $38.40 billion ($1,029.18 per capita) and a low estimate of $15.50 billion ($415.46 per capita). In all three scenarios, premiums paid by eligible individuals would generate $8.93 billion in annual revenues. After factoring in premiums, co-payments and the replacement of existing dental expenditures, the program’s net cost would be $6.01 billion in 2019, with an upper estimate of $15.09 billion and a lower estimate of negative $3.82 billion. Denticaid’s costs, including administrative costs, would be $15.09 billion ($404.49 per capita) in 2019, with a high scenario of $21.32 billion ($571.34 per capita) and a low scenario of $8.39 billion ($224.98 per capita). Denticaid’s premiums would generate less revenue to offset costs. The program’s net costs are estimated at $$7.47 billion in 2019, with a high estimate of $12.85 billion and a low estimate of $1.79 billion. There are additional challenges to consider, including dental office staffing levels in rural areas, dentists’ operating costs and orthodontic treatments. But none of this should prevent Canada from committing to a denticare program, which out-performs denticaid in terms of efficiency. Both federal and provincial governments would need to be involved in the necessary modifications to the Canada Health Act, with decisions on premiums and co-pays left to individual provinces. After those offsets, the remaining taxbased costs would be a relatively small increase in Canada’s public health spending and millions of Canadians would get access to good oral health.

With federal political parties increasingly interested in new options for dental services, it’s worth exploring two policy solutions to expand dental care into the public realm. Denticare would be a universal dental program for all Canadian residents. Denticaid would be a public dental insurance program for all Canadian children and uninsured adults. This paper estimates the costs of each option through micro-costing, which identifies the likely resources patients would use in each program and sums each unit cost in a given year to generate the estimated annual clinical cost. With no dental record-level information available for academic research, these estimates rely on survey data on oral health collected from across Canada. In particular, this paper uses the Canadian Community Health Survey (CCHS) and the Canadian Health Measures Survey (CHMS), both released by Statistics Canada. When neither survey contains the necessary data to inform assumptions and costing, data from similar high-income jurisdictions are used. Denticare’s costs are estimated using four key variables: the expected number of Canadians using dental services in a given year, the expected number of visits per year, the probability of dental treatments used per visit and the expected price of dental treatments. The first variable is based on Statistics Canada’s 2016 census data, multiplied by their 2019 overall provincial population estimates. The second relies mostly on the CCHS question “when was the last time you visited the dentist?” The third variable uses Australian data and the fourth integrates data from a variety of provincial dental fee guides. High, low and baseline cost scenarios are included, with each province and territory’s clinical costs projected five years after implementation in all three scenarios. To project future changes 1 in service costs, the rate of price increase is calculated from changes between the 2015 and 2019 suggested fee schedules. Methods for micro-costing the denticaid program are similar to the denticare model and the variables are mostly treated similarly. However, the population variable is manipulated to account only for individuals without private dental insurance. There are limitations to this approach. The CCHS is only a telephone survey and does not collect dental data from across every province. The lack of pan-Canadian service-level use data meant that data from an Australian survey was used in its place. This model could not account for the effects of income on the frequency with which any particular dental treatment category is accessed per visit. Australia also covers most dental treatments for children, so use of dental services could be higher than what could be expected in Canada. To obtain a more exact picture, provincial governments should try to collect service-level data on dental use and dental practice activity. However, this paper does provide Canadian policy-makers interested in exploring some sort of public dental care program with a rigorous estimation of the reimbursement of clinical costs for the options of both denticare and denticaid programs.

The 2019 MacKinnon report, commissioned by the Alberta government, recommended ending fee-for-service (FFS) as the model for paying primary care physicians because of its significant and inherent inefficiencies. Since then, the COVID-19 pandemic has also demonstrated the value of moving Alberta’s family physicians to an alternative payment (APP) model. While the MacKinnon report was in favour of enacting legislation to change the compensation model, this paper instead recommends offering physicians a choice of alternative payment programs as an incentive to move on voluntarily from an FFS system. Other provinces have attempted to reform physicians’ pay using a quadruple aim model for health-care improvement, which identifies the major points policy- makers must examine in instituting a replacement for FFS. The quadruple aim model is four-pronged and encompasses patient experience, population health, care team wellbeing and cost reductions. Alberta Health Services already uses the quadruple aim model to improve patient care and quality outcomes, although the MacKinnon report focused primarily on reducing costs. However, reforming doctors’ compensation is not just about the amount they should be paid; it must also consider that the method of compensation has a profound impact on both cost and quality of care received. Meanwhile, the self-isolation and social distancing measures for both doctors and patients, established with the arrival of the COVID-19 pandemic, have put Alberta’s doctors on a policy roller-coaster. Applying the FFS compensation model during the pandemic has resulted in the use of virtual care codes such as telehealth billing and in-person limited assessment codes. However, these codes were immediately problematic because they do not adequately account for complex patient care that requires longer visits, after-hours premiums and the Rural Remote Northern Program. During a pandemic is not the right time to embark on physician compensation reform. This gives the government time to reconsider the controversial approach taken prior to the COVID-19 pandemic. The need for compensation reform in Alberta is driven by the reality that Alberta has the highest proportion of physicians on FFS along with some of the highest FFS payments per physician in Canada. Meanwhile, family physicians in other provinces are now more likely to be covered by an APP rather than the former FFS system. The problem with FFS is that it tends to encourage physicians to create volume in number of patients seen per day, in order to increase compensation. Thus, it also encourages more diagnostic testing, which increases costs to the health-care system. In general, physicians compensated under FFS have much less incentive to consider costs when treating patients. The argument for legislating pay reform is poorly justified. No other province has legislated physicians out of the FFS system, and that is not a route Alberta should take, either. Nova Scotia has brought in a one-size-fits-all APP, while Ontario implemented a menu of higher paying APPs that produced greater downstream cost savings, making APPs an increasingly attractive payment option to family physicians. Ontario’s approach would be better for Alberta because it improves patients’ overall experience with primary care, their care outcomes and the wellbeing of those who care for the patients. Alberta should offer a menu of APP models tailored to primary care so that the family doctors themselves can choose the best model for their own practices. As this paper has demonstrated in its comparison of the experiences of other provinces, and as the COVID-19 affirms, the menu approach is the model most strongly aligned with the goals of quadruple aim.