Alternative Models Research Articles

Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.

Estimating the Allocation of the Economic Value Generated by Utilization of All-Oral Direct-Acting Antivirals for Hepatitis C in the United States, 2015–2019

ObjectivesBetween 2013–2019, several all-oral direct-acting antivirals (DAAs) were launched with the potential to cure patients with hepatitis C virus (HCV). They generated economic value in terms of the health gains for patients and cost-savings for the US healthcare system. We estimated the share of this value allocated to four manufacturers vs society. MethodsFor 2015–2019, we estimated the incremental impact of DAAs on HCV health outcomes and costs. We used the CDAF Polaris Observatory database to estimate utilization. Per-patient projections of lifetime quality-adjusted life-years (QALYs) gained and medical costs avoided were based on a standard 9-state HCV disease-progression model for DAA treatment vs alternatives. Annual QALY gains were valued at $114,000 per QALY. Outcomes and costs were discounted at 3%. Estimated revenues were based on reported sales. ResultsAn estimated 1,080,000 patients received DAAs: 81.5% would not have received the pre-DAA standard of care. On average, these patients were projected to gain 4.4 QALYs and save $104,400 in lifetime healthcare costs, generating $531.8 billion in value. Those who would have received treatment gained 1.7 QALYs and saved $41,500 in lifetime costs, generating $47.4 billion in economic value. As treatment costs fell nearly 75%, the four manufacturers reported $37.4 billion from DAA sales—an allocation of 6.5% of the total value. ConclusionsThe great majority (∼90%) of the economic value of curing HCV with DAAs were health benefits to patients and net cost-savings to society. DAA manufacturers received a minority share (6.5%) of the aggregate economic value generated.

Skull-Derived Myeloid Cells Augment T Cell Responses and Suppress Glioblastoma Growth

INTRODUCTION: Recent studies have implicated skull marrow as a functional myeloid reservoir in CNS pathology. However, its contribution to malignancy remains unexplored. METHODS: Fluorescently labeled calvarial flaps were transplanted onto syngeneic glioblastoma-bearing mice, followed by flow cytometric profiling of tumor-infiltrative leukocytes. To assay the functional relevance of SDMCs, tumor-bearing C57BL/6 mice were treated with preemptive calvarial ablation (13 Gy irradiation), or conversely intracalvarial AMD3100 to augment myeloid egress from marrow niches. Tumor burden was monitored via survival and bioluminescent imaging. RESULTS: 72 h following CMFDA-stained calvarial transplantation into tumor-bearing Balb/C mice, 40.3% of tumor-infiltrative myeloid cells were fluorescent and thus skull-derived; transplantation in an alternative longitudinal model (GFP+ flaps, C57BL/6) validated that SDMCs were robust and viable at 3 weeks post-operatively. As MHCII+ cells were disproportionately enriched among SDMCs (87.9% vs 67.3%, p = 0.012), we interrogated the immunogenicity of these cells through targeted ablation. Skull-ablated mice had reduced infiltration by antigen-presenting cells than controls (cDCs: 1.1% vs 4.5%, p = 0.002; macrophages: 14.4% vs 36.6%, p < 0.001) and 6-fold greater necrosis (67.7% vs 13.5% apoptotic, p < 0.001), suggesting an impaired ability to mount a controlled, adaptive immune response. The stimulatory role of SDMCs was further demonstrated via intracalvarial AMD3100 administration, which through its promotion of myeloid precursor egress (0.26% vs 0.02%, p < 0.001) and cDC2 infiltration (10.4% vs 3.0%, p = 0.003) yielded robust CD4+ T cell activation and effector memory differentiation. These differences were clinically meaningful, as skull irradiation accelerated tumor growth and attenuated survival compared to controls, while AMD3100 treatment accomplished the opposite (median OS: 17d vs 22d, p < 0.001; 26.5d vs 22d, p = 0.006). CONCLUSIONS: The preferential polarization of SDMCs into immunostimulatory APCs warrants the continued exploration of local marrow-targeting agents (e.g., AMD3100) as therapeutic modalities.

Improving student higher order thinking skills using SynecticHOTS-oriented learning model

The achievement of students’ learning outcomes in physics lessons has a low tendency, this is due to various factors, one of which is higher-order thinking skills (HOTS) based learning that has not been fully implemented in the learning process and assessment. This study aimed to determine the differences in the Synectic-HOTS learning model in physics compared to conventional learning models. This study used a quasi-experimental study with a pre-test–post-test nonequivalent control group design. The instrument used in this study is a two-tier test question that contains 20 items of HOTS aspect. The prerequisite test showed that the data was not homogeneous, while the results of the data homogeneity test were stated to be homogeneous. Therefore, a non-parametric test was carried out using the Mann-Whitney U-test. Based on the results of the data analysis, the Asymp. Sig. (2-tailed) for the pre-test was 0.111 and the post-test was 0.001 (p=.000<05). The effect size calculation shows that the Synectic learning model is effective in the medium category. These results indicate that the application of the SynecticHOTS model significantly improves HOTS when compared to conventional learning models. This work can open up insights to teachers about alternative, creative, and effective learning models to improve higher-order thinking skills and student learning outcomes.

Cultural mechanisms linking mothers' familism values to externalizing behaviors among Midwest U.S. Latinx adolescents.

This study was designed to examine associations among parents' familism values, adolescents' cultural resources, and externalizing behavior among Latinx youth in the Midwestern United States. Participants were 267 Latinx adolescents (M age = 15.58 years; SD = 1.28 years; 45% girls; 82.8% Mexican American) and their mothers/mother figures who completed individually administered interviews comprised of standardized measures. Structural equation modeling was used to test several alternative mediational models in which youth ethnic identity and familism values served as potential cultural mechanisms linking parents' familism values to lower levels of youth externalizing behavior. Results showed that mothers' familism values were positively associated with youth ethnic identity which was positively associated with youth familism values; in turn, youth familism values were inversely associated with externalizing behavior. The findings did not differ by youth gender or nativity (U.S.-born vs. foreign-born youth). These findings provide support for cultural resilience perspectives by highlighting the protective role of ethnic identity and familism values among U.S. Latinx adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A theoretical framework for the analysis of an opposed piston linear engine design

Traditional crank-based engines face limitations due to mechanical, thermal, and combustion inefficiencies. In contrast, the opposed piston design of a linear engine generator mitigates frictional losses by eliminating rotational motion and crankshaft linkages. Instead, electrical power is generated through the oscillation of a translator within a linear stator. However, the lack of geometric constraints in the free piston design leads to uncertainties regarding dead center positions, resulting in challenges such as misfire, stall, over-fueling, and rapid load changes.This study aims to fill this gap by reviewing existing modeling literature and advancing the fundamental understanding of opposed piston linear engines (OPLE) with springs through the development of an idealized, nondimensional model. A combination of analytical and numerical models was developed to better understand the behavior of the OPLE. The model introduces a streamlined symmetric analytical solution, succeeded by a broader general analytical resolution, with careful attention to the significant influence of thermodynamic effects at each phase, offering insights into the engine's dynamic performance. Limitations inherent to the analytical solutions are addressed by a numerical scheme utilizing the Runge-Kutta technique. This approach guarantees swift and dependable computational outcomes, which captures cyclic variation. The alternator model amalgamates both linear and sinusoidal work profiles, adjusting the magnetic work output in response to fluctuations in the compression ratio relative to the Top Dead Center (TDC) clearance distance. This adjustment dictates the generator load for each translator.The proposed model integrates the dynamics of a damped spring-mass system with thermodynamic expressions representing in-cylinder processes. Simplifications are made assuming perfect springs, ideal gases, instantaneous heat transfer, and an average friction force dependent on stroke length for work output. Selected cases are analyzed to elucidate the system's fundamental behavior, both within and outside the context of the Otto cycle, showcasing natural and forced stability over multiple operation cycles. Notably, enhancing the baseline cylinder pressure, or input heat relative to spring stiffness can elevate the work-to-heat ratio values. The attained work-to-heat ratio within compression ratio window of 16 is approximately 28 %. While this percentage may fluctuate in the context of general FPLE designs, the model developed for OPLE in this work plays a crucial role in maintaining the engine within this narrowly defined efficiency range, without compromising the potential performance demonstrated in this study. Differences in compression ratios provided intriguing insights into the dynamics of the translator and the in-cylinder thermodynamics of the interconnected system. Lower TDC clearance resulted in high translator displacement, velocity, and enhanced thermal efficiency.

Wisdom predicts emotional intelligence and wise reasoning

ABSTRACT In a recent article in The Journal of Positive Psychology, Schneider et al. (2023) examined the relations of emotional intelligence (EI) on wise reasoning and three-dimensional wisdom. They concluded that only the managing emotions branch of EI predicted wise reasoning, contingent upon epistemic humility and need for cognition in Study 1 (N = 99) and epistemic humility, empathic concern, and perspective taking in Study 2 (N = 150). Unfortunately, this article has several problems, including (a) the mischaracterization of three-dimensional wisdom as knowledge rather than personality qualities, (b) mediating variables whose concepts and measures partially overlapped with wise reasoning and wisdom, and (c) some problems with computing the three-dimensional wisdom scale (3D-WS) in Study 2. I tested alternative path models, which showed that three-dimensional wisdom predicted EI and wise reasoning, whereas EI by itself did not predict wise reasoning. Wise reasoning might depend more on personal wisdom than EI.

Two-sample test for stochastic block models via the largest singular value

The stochastic block model is widely used for detecting community structures in network data. However, the research interest in much of the literature focuses on the study of one sample of stochastic block models. Detecting the difference between the two community structures is a less studied issue for stochastic block models. In this article, we propose a novel test statistic based on the largest singular value of a residual matrix obtained by subtracting the geometric mean of two estimated block mean effects from the sum of two observed adjacency matrices. We prove that the null distribution of the proposed test statistic converges in distribution to the Tracy-Widom distribution with index 1, and we show the difference between the two samples for stochastic block models can be tested via the proposed method. We show that the proposed test is asymptotically powerful against alternative models. Further, we extend the proposed method to the degree-corrected stochastic block model. Both simulation studies and real-world data examples indicate that the proposed method works well.

Embodied and embedded mindfulness: a mindful path to well-being

ABSTRACT While there is a growing interest in mindfulness as an intrapersonal trait, only a limited number of studies have investigated interpersonal mindfulness, and no study has examined the interaction between both concepts. This paper aims to evaluate a path model that depicts the role of both intrapersonal and interpersonal mindfulness in facilitating emotion regulation and improving well-being by mitigating the effects of psychological symptoms and enhancing social connectedness and safeness. Additionally, this study aims to compare the results obtained using different measures of intrapersonal and interpersonal mindfulness. Moreover, the study evaluates an alternative path model. A sample of 353 participants completed various measures of intrapersonal and interpersonal mindfulness, emotion dysregulation, psychological symptoms (stress, anxiety, and depression), social connectedness, social safeness, satisfaction with life, and happiness. The findings supported the proposed path model, indicating that emotion regulation mediated the relationship between intrapersonal and interpersonal mindfulness on one side and psychological symptoms and social connectedness and social safeness on the other side. Furthermore, the findings suggested that psychological symptoms and social related measures mediated the associations between emotion regulation and well-being. The same path model was supported when using different sets of mindfulness measures. The alternative path was not supported. This study enhances our understanding of how intrapersonal and interpersonal mindfulness interact together to promote emotion regulation, improve well-being, mitigate psychological symptoms, and foster social relatedness and safeness. The findings highlight the importance of training both intrapersonal and interpersonal mindfulness skills to enhance well-being. Implications and limitations are thoroughly discussed.

New reimbursement models to promote better patient outcomes and overall value in laboratory medicine and healthcare.

The most widespread healthcare reimbursement models, including diagnostic laboratory services, are Fee-for-Service, Reference Pricing and Diagnosis-Related Groups. Within these models healthcare providers are remunerated for each specific service or procedure they operate. Healthcare payers are increasingly exploring alternative models, such as bundled payments or value-based reimbursement to encourage value of patient care rather than the simple amount of delivered services. These alternative models are advised, as they are more efficient in promoting cost-effective, high-quality laboratory testing, thereby improving patient health outcomes. If outcomes-based evaluation is a pillar in a new vision of "Value-Based Healthcare", an active policy of Value-Based Reimbursement in laboratory medicine will assure both an efficiency-based sustainability and a high-quality effectiveness-based diagnostic activity. This review aims to evaluate current and alternative reimbursement models, to support a wider agenda in encouraging more Value-Based Healthcare and Value-Based Reimbursement in laboratory medicine.

A finite volume scheme for solving an alternative morphodynamic model with porosity

AbstractThis work proposes an extended numerical scheme based on the finite volume method that is intended to solve a new morphodynamic model with porosity. The St-Venant equations and the Exner equation are coupled in this model, accounting for the variation of the porosity function . In the morphodynamic system, the Jacobian matrix's sign is taken into account when reconstructing the numerical fluxes using an improved Roe's approach to assure correct numerical computations.

Autonomy in Eating Disorder Treatment and Recovery (Emerald Full Text).

Abstract Purpose: This study has two aims: the first is to develop a rich and nuanced understanding of autonomy informed by lived experience data from peer-reviewed studies in the Eating Disorder literature; the second is to examine how experiences of autonomy influence treatment and recovery. Background: Eating Disorders are of significant concern, affecting approximately 9% of the global population and have the highest mortality rate of any mental health disorder (Arcelus, Mitchell, Wales and Nielsen 2011). Even the most effective interventions fail to benefit a substantial number of people, with a projected trajectory of enduring disability in 20-30% of Eating Disorder cases internationally (Strand 2021: 19). On average, recovery from an Eating Disorder lasts from one to six years (Butterfly Foundation 2015: 16). Despite these concerning statistics, current understandings of autonomy are individualistic, with treatment practices exerting external control and influence, rather than supporting autonomy. Furthermore, the absence of trauma acknowledgment likely affects how people with lived experience of an Eating Disorder, and their treatment providers, negotiate treatment and recovery goals. Research Design: A rapid evidence assessment was conducted to answer the research question: How do we understand the autonomy of people with lived experience of an Eating Disorder, and what does this mean for their treatment and recovery?. A systematic search of five electronic databases, the International Journal of Eating Disorders, and topic-specific grey literature from 2000-2021 was undertaken. Twenty articles were deemed eligible for inclusion in the study. Interpretive phenomenological analysis was undertaken to inform the key findings and discussion. Findings and Discussion: The researcher identified four central themes: Self versus Eating Disorder, Self in Treatment, Self in Recovery, and Others in Relation to Self. These themes enabled rich re-conceptualisation of autonomy, identifying a recursive Lack of Autonomy Loop affecting many clients currently being treated for Eating Disorders, and under-researched aspects of autonomy including relational factors and the absence of trauma-informed approaches for (re) establishing autonomy. Conclusion: Research findings illuminate the shortcomings of current treatment models, provide options for alternate models, generate implications for social work practice and offer direction for future research and necessary policy change.

The relationship between bullying victimization and impairment in personality functioning in a clinical adolescent sample.

Problematic interpersonal relationships may represent both, a risk factor for the development or trigger of personality disorder (PD) symptoms and its consequences. Since peer relationships become more and more important in adolescence, the current study explores the cross-sectional association between recent bullying experiences and levels of impairment in personality functioning according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) alternative model of personality disorders (AMPD; Criterion A) in help-seeking adolescents (N = 493). Logistic and multiple regression analyses revealed that patients who were frequently bullied in the past 3 months (i.e., at least once a week) were more likely to reach the diagnostic threshold for PD according to the AMPD (OR = 1.71, p = .025) and showed higher levels of impairment in identity (β = .41, p < .001), empathy (β = .26, p = .002), and intimacy (β = .30, p = .001), but not self-direction, compared to patients who did not report any bullying experiences. Occasional bullying in the past 3 months (i.e., every few weeks) was neither associated with a greater likelihood to reach the diagnostic threshold for PD nor with greater impairments in identity, self-direction, empathy, or intimacy compared to no bullying. While the current study provides support for a correlation between bullying experiences and personality dysfunction (particularly in the elements identity and intimacy), longitudinal research is needed to clarify whether experiences of bullying cause or trigger personality dysfunction or/and vice versa. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluating Airborne Sound Insulation in Dwellings Constructed with Hollow Ceramic Blocks under Brazilian Housing Policies

In Brazil, there is a shortage of approximately 5.80 million residences, a challenge that intensified during the pandemic. Since 2013, there has been a mandate to implement specific performance criteria in residential constructions. However, many construction firms face difficulties in meeting these standards, especially concerning sound insulation in partition elements. This work aims to assess the airborne sound insulation performance and compliance with legal standards in new residential buildings through measurements and simulations. In particular, subsidized housing units for low-income populations are studied, which are eligible for reduced taxes on building loans. These buildings are typically made of hollow ceramic blocks with vertical perforations as separating walls, a commonly used national building material. Three buildings located in Guarapuava, a southern city in Brazil with a population of approximately 183,000 residents, were selected for this purpose. Measurements were conducted following ISO 16283-1 guidelines, whereas simulations were performed using ISO 12354-1, initially assuming a uniform plate but also exploring an alternative model that considers orthotropic behavior with analytical expressions. The calculations considered both static and dynamic moduli of elasticity. The results indicated that all the units failed to meet the specified standards. The measured DnT,w values were below the required thresholds, obtaining 42 &lt; 45 dB for Building B1, 40 &lt; 45 dB for Building B2, and 38 &lt; 40 dB for Building B3. The predicted DnT,w values agreed well with the measured values when considering orthotropy with a dynamic elastic modulus. However, discrepancies were observed in the spectral analysis, especially at lower and higher frequencies. The findings suggest refraining from employing single-leaf partition walls made of vertical hollow ceramic blocks in such buildings. Improving sound insulation necessitates embracing a comprehensive strategy that takes into account the separating element, flanking paths, and the room geometries.

Stories Sit in Places: News Media Representations and Social Development Communication of the Protesting Farmers in Central Mindanao, Philippines of the Kidapawan Massacre

This study explored the media representations of farmer-victims in Kidapawan City, the Philippines. Specifically, this examined how Metropolis-based news media represented the farmers who were reportedly involved in socio-political issues with the government that paved the way to the Kidapawan Massacre dated 1 April 2016. Juxtaposed with the exploration was the examination of how the oppressed and marginalised group was presented in media reports within the context of social development. This researcher employed van Dijk’s (1998, A critical discourse analysis) Critical Discourse Analysis of selected 27 tabloid news stories. This critical research led to the way of thinking that because of the government’s inaction and the media’s neoliberal-capitalistic ideology, farmers’ plight was overlooked and silenced. In this elite-dominated Philippine society as well as in the Asia-Pacific, discourses of people-centred development were relatively scant and torpid. Hence, the conceptualisation of an alternative model, that is Communication and Social Development ( Pascual, 2018 : Media representations of the Kidapawan farmers and social development communication in the Kidapawan Massacre).

The heterogeneous impacts of environmental technologies and research and development spending on green growth in emerging economies: the moderating role of financial globalization

Introduction: Understanding the heterogeneous impacts of environmental technologies (ETs), research and development (RD) spending and financial globalization (FG) on green economic growth (GEG) is worthwhile to promote progress toward GEG. Besides, exploring the moderating role of FG is essential to uncover the nuanced dynamics that shape the relationship between ET, RD, GEG, and the influence of global financial integration. Thus, this study examines the effects of ET, RD and FD on GEG in emerging market economies (EMEs). In addition, we investigate the moderating role of FG on the effects of ETs and RD on GEG.Methods: The method of moments quantile regression (MMQR) is applied using a fixed effects model that can capture distributional heterogeneity and nonnormality concerns for the panel of 25 EMEs from 2000 to 2019. In addition, other alternative models are applied to conduct robustness analysis. We use green total factor productivity (GP) to proxy for GEG using the Malmquist–Luenberger Productivity Index (MLPI) strategy based on the directional distance function (DDF).Results and discussion: The findings imply that ETs significantly impact GEG, revealing evidence that promoting environmental innovation positively contributes to GEG progress in EMEs. Likewise, RD promotes GEG progression in EMEs. Additionally, FG positively impacts GEG. FG also positively moderates the effects of ETs and RD on GEG, implying that countries open to FG can better harness the positive roles of investment in ETs and RD on GEG in EMEs. Therefore, policymakers should develop prudent policies to encourage ETs and RD to promote GEG in EMEs, which aligns with the goals of controlling climate variation (SDG-13) and fostering innovation (SDG-9) to promote GEG in EMEs.

The expression of sehnsucht in the Japanese city pop revival fandom through visual media on Reddit and YouTube

Japanese city pop music, which emerged in the late 1970s through the late 1980s, saw a resurgence in interest in the late 2010s as an online revival fandom formed across multiple platforms. This emergent fandom has prompted scholars to ask why this fandom emerged and how this audience relates to music disconnected in time and place from themselves. Various forms of qualified nostalgia have been suggested to describe different modes of engagement with media of the past, although these terms are both semantically awkward and do not capture the case of engagement with media removed from the personal or generational past. However, sehnsucht, an alternative model of evaluating the past against the present, is better suited to describing the mode of connection between fans, music, and the past. A thematic analysis of visual media in a case study of conversations on the r/citypop subreddit and on YouTube reveals that city pop fans seem to cluster many of the themes of sehnsucht in their relationship to a musical genre from an idealized past removed from the austere present.

The role of basic psychological needs satisfaction (BPNS) during the initial use of online teaching platforms on faculty members’ continuance intention

PurposeBased on self-determination theory (SDT), this study aims to investigate the motivational antecedents of faculty members’ continuance intention of using online teaching platforms. For this purpose, we introduced a model incorporating basic psychological needs satisfaction (BPNS) and different motivational mechanisms.Design/methodology/approachUsing a survey study of 312 faculty members, we examined the model by structural equation modeling (SEM).FindingsThe SEM results revealed a positive correlation between BPNS and continuance intention. Additionally, we illustrate the importance of different types of extrinsic motivation. By presenting an alternative model, we demonstrate that the initial-use-identified regulation (one type of extrinsic motivation) has an association with continuance intention (CI). However, this association loses significance if BPNS is present within the model. Moreover, we determined that there is no significant relationship between initial-use external regulation (another type of extrinsic motivation) and faculty members' CI for online teaching. Lastly, the results revealed that pre-use amotivation and intrinsic motivation impact CI through initial-use BPNS.Research limitations/implicationsThe results suggest that decision-makers at educational institutions should consider that extrinsic motivation has different types with different impacts and that BPNS has a vital role in faculty members’ intention to continue using online teaching platforms.Originality/valueThis study is novel because it reveals some details of extrinsic motivation effects by offering a model that combines BPNS and different types of motivation in two stages. It is important and rare that we concentrate on the almost neglected issue of faculty members’ motivational perspectives in online teaching, while the literature mainly focuses on students’ perspectives.

Cost-effectiveness of nivolumab versus surveillance for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence: a US payer perspective

ABSTRACT Aim To evaluate the cost-effectiveness of adjuvant nivolumab compared with surveillance for the treatment of patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection from a US healthcare payer perspective and to investigate the impact of alternative modeling approaches on the cost-effectiveness results. Material and Methods A four-state, semi-Markov model consisting of disease free, local recurrence, distant recurrence, and death health states was developed to investigate the cost-effectiveness of nivolumab compared with surveillance over a 30-year time horizon. The model used data from the randomized CheckMate 274 study (NCT02632409) and published literature to inform transitions among health states, and inputs on cost, utility, adverse event, and disease management. Scenario analyses were conducted to investigate the impact of model structure and key assumptions on the results. One-way deterministic and probabilistic sensitivity analysis were conducted to investigate the robustness of the results. Results Total expected costs were higher with nivolumab ($162,278) compared with surveillance ($63,027). Nivolumab was associated with improved survival (1.61 life-years gained compared with surveillance) and an incremental gain of 0.98 quality-adjusted life-years (QALYs). Although total treatment costs were higher for nivolumab, cost offsets were observed because of delayed or avoided recurrences and deaths experienced with nivolumab compared with observation. The incremental cost-effectiveness and cost-utility ratios were $61,462/life-year and $100,930/QALY. Limitations At the time of analysis, CheckMate 274 had limited follow-up on disease-free survival and no overall survival data. The limited evidence necessitated assumptions on modeling survival after each type of recurrence. Conclusions Nivolumab is estimated to be a life-extending and cost-effective option for adjuvant treatment of MIUC for patients who are at high risk of recurrence after undergoing radical resection in the United States. Using a threshold of $150,000/QALY, the cost-effectiveness conclusions remained consistent across the scenario and sensitivity analyses conducted.

An alternative model of process damping in milling based on Hertz theory

An alternative model of process damping in milling based on Hertz theory