University of Puget Sound

Background Biologic (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis (RA) target inflammatory pathways implicated in the pathogenesis of multiple myeloma (MM). It is unknown whether use of b/tsDMARDs affects the incidence of MM. Methods In this cohort study using Veterans Health Administration (VHA) data, we identified Veterans newly diagnosed with RA from 1/1/2002 to 12/31/2018 using diagnostic codes and medication fills. DMARD exposure was categorized as follows: conventional synthetic (cs)DMARDs; bDMARDs, which included tumor necrosis factor inhibitors (TNFi), non-TNFi; and a tsDMARD, tofacitinib. A Cox proportional hazards model with time-varying exposure was used to estimate the hazard ratio for developing MM among those who received b/tsDMARD medications relative to b/tsDMARD-naïve persons. Results 27,540 veterans with RA met eligibility criteria of whom 8322 (30%) took a b/tsDMARD during follow-up. There were 77 incident cases of MM over 192,000 person-years of follow-up. The age-adjusted incidence rate (IR) of MM among b/tsDMARD-naïve patients was 0.37 (95% CI 0.28–0.49) per 1000 person-years and 0.42 among current or former b/tsDMARD users (95% CI 0.25–0.65). Adjusting for age and other demographic characteristics, the hazard ratio for MM associated with use of b/tsDMARDs was 1.32 (95% CI 0.78, 2.26). Conclusion In this study of Veterans with RA, the rate of MM did not differ between b/tsDMARD and csDMARD users. The relatively short duration of follow-up and few events limited our power to detect treatment-related differences in MM risk.

Should you take a pill that gives you all the health benefits of sleep and allows you to stay awake? I argue that you shouldn’t. I propose three reasons why sleeping, conceived of as a socially and culturally embedded human activity, is valuable. First, there is aesthetic value in the rituals that typically precede sleeping; second, there is interpersonal value in the intimacy that stems from sleeping with other people; third, there is ethical value in mere presence and in retreating from consciousness. In order to fully support my argument, I situate it within a conception of goodness that embraces the fragility of the human condition and the limitations stemming from our corporeal nature. I conclude with some practical implications of my view.

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD). A four-class machine-learning algorithm was trained using age and nine sleep biomarkers from patients with clinically-diagnosed manifest and prodromal NDDs, including Alzheimer’s disease dementia (AD = 27), Lewy body dementia (LBD = 18), and isolated REM sleep behavior disorder (iRBD = 15), as well as a control group (CG = 58). The algorithm was validated in a total of 381 recordings, which included the training data set plus an additional AD = 10, iRBD = 18, Parkinson disease without dementia (PD = 29), mild cognitive impairment (MCI = 78) and CG = 128. Test–retest consistency was then assessed in LBD = 10, AD = 9, and CG = 46. The agreement between the NDD profiles and their respective clinical diagnoses exceeded 75% for the AD, LBD, and CG, and improved when NDD participants classified Likely Normal with NDD indications consistent with their clinical diagnosis were considered. Profiles for iRBD, PD and MCI participants were consistent with the heterogeneity of disease severities, with the majority of overt disagreements explained by normal sleep characterization in 27% of iRBD, 21% of PD, and 26% of MCI participants. For test–retest assignments, the same or similar NDD profiles were obtained for 88% of LBD, 86% in AD, and 98% of CG participants. The potential utility for NDD subtyping based on sleep biomarkers demonstrates promise and requires further prospective development and validation in larger NDD cohorts.

Economists have typically viewed an individual's economic choices as being tightly linked to their preferences, and in turn, their preferences being tightly linked to the welfare associated with those choices. But behavioral economics drove a wedge between choice and preference, and thus, in turn, between choice and welfare. Trying to reconcile the choice-preference-welfare relationship came to be called the reconciliation problem and one of the main approaches to the problem has been called preference purification. But the presumption has been that preference purification only became an issue with the rise of behavioral economics. This paper will argue that is not the case. During the first part of the twentieth century when the ordinal utility theory of consumer choice was still in the early stages of development, there were many economists who thought about preferences in ways that were quite similar to the way that preferences have been characterized in recent debates about preference purification. This paper will discuss the history of this literature in a way that emphasizes the difference between the situational context of this early research on ordinal utility and the quite different situational context of the recent debates on preference purification. The conclusion suggests how these differences in situational context prevented the similarities between the two literatures from being recognized.

Connectivity is integral to the dynamics of metapopulations through dispersal and gene flow, and understanding these processes is essential for guiding conservation efforts. Abalone, broadcast‐spawning marine snails associated with shallow rocky habitats, have experienced widespread declines, and all seven North American species are threatened. We investigated the connectivity and population genomics of pinto/northern abalone (Haliotis kamtschatkana), the widest‐ranging of abalone species. We employed reduced representation sequencing (RADseq) to generate single nucleotide polymorphism (SNP) data, assessing population connectivity and potential adaptive variation at 12 locations across the full range from Alaska to Mexico. Despite depleted populations, our analysis of over 6000 SNPs across nearly 300 individuals revealed that pinto abalone maintains a high genetic diversity with no evidence of a genetic bottleneck. Neutral population structure and isolation by distance were extremely weak, indicating panmixia across the species' range (global FST = 0.0021). Phylogenetic analysis, principal components analysis, and unsupervised clustering methods all supported a single genetic population. However, slight population differentiation was noted in the Salish Sea and Inside Passage regions, with evidence for higher barriers to dispersal relative to outer coastal areas. This north‐central region may also represent the species' ancestral range based on relatively low population‐specific FST values; the northern and southern extremes of the range likely represent range expansions. Outlier analysis did not identify consensus loci implicated in adaptive variation, suggesting limited adaptive differentiation. Our study sheds light on the evolutionary history and contemporary gene flow of this threatened species, providing key insights for conservation strategies, particularly in sourcing broodstock for ongoing restoration efforts.

Purpose Heart rate variability (HRV) has been used for decades as a tool for measuring systemic health through the autonomic nervous system (ANS). The purpose of this paper was to examine the literature on HRV and to investigate its use in the long COVID (LC) population. Summary of Key Points Measurement devices vary significantly in their validity and reliability when compared with the gold standard of electrocardiogram (ECG). Wrist and hand devices typically demonstrate diminished validity for capturing HRV signal, while chest strap devices often exhibit high reliability and validity. Lack of transparency in third-party software used to clean and analyze HRV data makes assessment for accuracy problematic. This is of particular concern when single beat miscalculations can result in significantly dissimilar output. The conditions under which HRV data are collected, such as natural or paced breathing, activity intensity, and patient position, can dramatically affect HRV readings. While some individual HRV metrics have consistently been shown to reflect certain components of the ANS, such as high-frequency power as a measure of parasympathetic function, the meaning of other metrics is less clear. Recommendations for Clinical Practice Heart rate variability can be an extraordinarily valuable tool to measure systemic function. However, it is recommended that clinicians be judicious in the interpretation of HRV, considering inconsistencies in presentation. This is particularly true in LC, where individual HRV varies greatly. In all populations, clinicians should consider using valid devices to assess trends in HRV values over time, along with consideration of unique physical conditions.

We study the large field limit in Schrödinger equations with magnetic vector potentials describing translationally invariant B-fields with respect to the z-axis. In a first step, using regular perturbation theory, we derive an approximate description of the solution, provided the initial data are compactly supported in the Fourier variable dual to $z\in {{\mathbb {R}}}$. The effective dynamics is thereby seen to produce high-frequency oscillations and large magnetic drifts. In a second step, we show, by using the theory of almost invariant subspaces, that this asymptotic description is stable under polynomially bounded perturbations that vanish in the vicinity of the origin.

Motivated by her interest in fabric arts, late-eighteenth-century British chemist Elizabeth Fulhame experimentally investigated whether cloths of gold, silver, and other metals could be made by chemical rather than mechanical processes. In contrast to other women studying science at this time, she not only published an original monograph under her own name that challenged both the phlogistic and antiphlogistic views of combustion but also proposed an alternative explanation for oxidation and reduction. Although her contemporaries widely cited her innovative research, her history is not well known, yet a careful analysis of her work provides further insights into the reception of the antiphlogistic theory and the challenges and limitations experienced by women in chemistry during this period.

The habitat heterogeneity hypothesis posits that diversity should increase with greater variation in environments. In old growth temperate rainforests, a high degree of habitat heterogeneity is created by an abundance of large nurse logs and woody debris that may influence patterns of diversity. We examined how the structural heterogeneity of the forest understory at a microtopographic scale affects the diversity of understory plants and lichens in the Hoh rainforest, Washington using rugosity as a measure of heterogeneity. We examined habitat associations and community structure of species among substrate types using null models. We found a hump shaped relationship between rugosity and species diversity. This was due to dominance by nonvascular plants in areas with high rugosity created by the specialization of bryophyte species to nurse logs, and dominance by vascular plants in areas with low rugosity created by the specialization of vascular plant species to the forest floor. The redundancy of substrate types where rugosity levels were both low and high caused the mid-levels of rugosity to have the highest habitat heterogeneity and subsequently the highest species diversity. Bryophyte species dominated this system making up 57% of the 54 species surveyed, followed by angiosperms (18%). More species were specialized to nurse logs than the forest floor. Our study revealed that the habitat heterogeneity-diversity relationship is supported in old growth temperate rainforests. We found that nurse logs are keystone structures that provide unique habitats for bryophytes, and shape both the structure of the understory and overall plant community dynamics in these forests.

Purpose: Resilience, the ability to maintain or restore baseline function after a stressor, remains unexplored in patients with bladder cancer. Our objective was to demonstrate the feasibility of prospectively characterizing baseline resilience, related psychological resources, and frailty in patients with bladder cancer and evaluate associations with quality-of-life and mental health outcomes over time. Materials and methods: We enrolled patients with bladder cancer (N = 67, September 2020-July 2021) into a prospective, observational, cohort study. At intake, patients completed validated assessments of frailty domains and psychological resources (resilience, psychological capital, self-compassion, and thriving, collectively PsyResources). Validated quality-of-life surveys were completed at 2 weeks, 3 months, and 6 months after treatment selection. Correlation matrices were constructed to quantify correlations between baseline PsyResources and frailty measures (reported with Spearman correlation coefficient [ρ]). Associations between PsyResources and quality-of-life outcomes were evaluated with linear regression. Results: The median age was 71 years (83.6% male), and 77.6% had muscle-invasive bladder cancer (cN+: 21%, M1: 7.6%). Baseline PsyResources were inversely correlated with the Geriatric Depression Scale (ρ = -0.50 to 0.65, P < .0001). Higher baseline PsyResources were associated with improved global symptoms and emotional function and decreased anxiety and depression over time (B: -0.17 to -2.5; P < .05). Conclusions: We present the first prospective characterization of baseline PsyResources in patients with bladder cancer. We observed positive correlations with improved mental health and quality-of-life outcomes over time. Ongoing work is exploring the relationship between resilience, frailty domains, and their role in functional recovery after treatment. Future work is needed to understand associations between PsyResources and treatment tolerance, recovery trajectories, and oncologic outcomes.

Objectives Chronic pain disorders are among the most common and affect approximately 20% of the US population, leading to disproportionately high medical expenditures and negative economic impact. Behavioral factors of pain catastrophizing and perceived injustice are associated with pain intensity in chronic pain. Diminished heart rate variability (HRV) is also strongly associated with chronic pain. These factors have been less explored earlier in the pain experience and it is unclear whether they play a role in the transition from acute to chronic pain. The aim of this study was to determine the relationship between pain catastrophizing, perceived injustice, pain intensity and HRV in naturally occurring acute pain. Methods Ninety-seven subjects were recruited from local outpatient physical therapy clinics. Seated HRV was captured on ninety-four subjects via Polar chest strap while subjects were taking a survey via iPad. In addition to sociodemographic data, the survey included the Pain Catastrophizing Scale (PCS), Injustice Experience Questionnaire (IEQ), and Numeric Pain Rating Scale (NPRS). The natural log of high frequency power (lnHFP) HRV was used in the statistical analysis. Results Multiple regression modeling revealed that lower pain catastrophizing, higher perceived injustice, and lower pain intensity were associated with lower HRV, and accounted for 11.4% of the variance in HRV. Discussion While greater chronic pain intensity is associated with lower HRV, the relationship is reversed in the setting of acute pain. These findings highlight the need to better understand the unique factors that contribute to lower HRV in the acute phase.