Dartmouth College
  • Hanover, NH, United States
Recent publications
This chapter provides insight into the history and status of blended care (BC), a rapidly evolving treatment alternative for mental health and substance use disorders that integrates elements of psychological therapy and digital therapeutics. How do we unlock the enormous potential of BC and scale it to the healthcare system? To this end, we first define what comprises BC, discuss its value to field, and highlight the challenges that confront efforts to expedite its translation from client, provider, and health systems perspectives. Rapid technological advancements and a growing number of clinical applications provide exciting opportunities for improving access to care and optimizing outcomes, but complicate efforts to demonstrate efficacy and disseminate evidence-based recommendations. We describe the continuum of BC options offered to support distinct client populations, including examples of innovative solutions being used around the globe. We conclude with future directions for advancing BC and promoting the integration into healthcare services.
Mental health and substance use disorders are highly prevalent and are the leading cause of global disease burden worldwide. Nevertheless, most persons with mental health or substance use disorders do not receive care. Prominent barriers to traditional care include (1) stigma, (2) lack of culturally competent treatments, (3) prohibitively high cost and lack of insurance coverage, (4) inability to attend appointments due to transportation or available appointment times, and (5) inability to find coverage and prohibitively long wait times resulting from structural problems with an inadequate number of mental health providers. With the proliferation of the internet and mobile phones, digital therapeutics (software designed to prevent, treat, or manage a medical disorder or disease) are fundamentally able to address these issues. As digital therapeutics are (1) scalable, (2) constantly accessible, (3) less stigmatizing, (4) cost-effective, and (5) culturally adaptable, digital therapeutics are poised to transform mental health and substance use care.
The weldability and effects of subsequent heat treatment on the microstructure and mechanical properties of the medium-entropy alloy (MEA) (NiCoCr) 94 Al 3 Ti 3 have been explored using electron beam welding (EBW). It was found that EBW joints consist of a supersaturated f.c.c. matrix with coarse, asymmetric columnar grains (17.7-24 μm). The fraction of twins and Σ3 n CSL boundaries in weld joints was only 10% of that in the base metal, a value which increased to 30% after aging at 800 • C. The aging also led to improvements in the hardness, tensile strength, and work hardening rate, a result of the precipitation of a high volume fraction (0.29-0.33) of ultrafine (15-17.4 nm dia.) coherent spherical L1 2-structured particles. The contributions of the L1 2 nano-particles and Hall-Petch strengthening to the yield strength were estimated to be 537-573 MPa and 105-123 MPa, respectively. The MEA shows excellent weldability and, after aging, good strength (YS~1098 MPa, UTS~1368 MPa) and elongation to failure (~11%) by ductile fracture.
Background Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC. Methods and results We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients ( N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97–1.00; CD8T: HR = 0.97, 95% CI = 0.95–1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00–1.07; mdNLR: HR = 1.12, 95% CI = 1.04–1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death ( P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites. Conclusions Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.
Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, there has been limited opportunity to compare the effect of different adjuvants on these activities in humans. Here, samples from the AVEG015 study, a phase 1 trial in which participants ( n = 112) were immunized with gp120 SF-2 and one of six different adjuvants or combinations thereof were assessed for antibody titer, biophysical features, and diverse effector functions. Three adjuvants, MF59 + MTP-PE, SAF/2, and SAF/2 + MDP, increased the peak magnitude and durability of antigen-specific IgG3, IgA, FcγR-binding responses and ADCP activity, as compared to alum. While multiple adjuvants increased the titer of IgG, IgG3, and IgA responses, none consistently altered the balance of IgG to IgA or IgG3 to IgA. Linear regression analysis identified biophysical features including gp120-specific IgG and FcγR-binding responses that could predict functional activity, and network analysis identified coordinated aspects of the humoral response. These analyses reveal the ability of adjuvants to drive the character and function of the humoral response despite limitations of small sample size and immune variability in this human clinical trial.
The present study investigated the microstructure, nanomechanics, and corrosion behavior of AlCoCuFeNi high entropy alloys fabricated by selective laser melting (SLM) and laser metal deposition (LMD). The microstructure of SLM-processed specimens was mainly composed of columnar-grained BCC matrix (∼90 µm in width) and Cu-rich twinned FCC phase. The columnar grains grew epitaxially along the building direction and exhibited a strong {001} texture. In comparison, a coarse columnar-grained BCC matrix (∼150 µm in width) with a stronger 〈001〉 texture, rod-like B2 precipitates, and large core-shell structured FCC phases were formed in the LMD-processed specimens due to the higher heat accumulation effect. Consequently, the LMD-processed specimens showed a lower hardness, wear resistance, and corrosion resistance, but higher creep resistance and reduced Young's modulus than the SLM-processed specimens. Hot cracks occurred in both types of specimens, which could not be completely suppressed due to Cu segregation.
Though cell size varies between different cells and across species, the nuclear-to-cytoplasmic (N/C) ratio is largely maintained across species and within cell types. A cell maintains a relatively constant N/C ratio by coupling DNA content, nuclear size, and cell size. We explore how cells couple cell division and growth to DNA content. In some cases, cells use DNA as a molecular yardstick to control the availability of cell cycle regulators. In other cases, DNA sets a limit for biosynthetic capacity. Developmentally programmed variations in the N/C ratio for a given cell type suggest that a specific N/C ratio is required to respond to given physiological demands. Recent observations connecting decreased N/C ratios with cellular senescence indicate that maintaining the proper N/C ratio is essential for proper cellular functioning. Together, these findings suggest a causative, not simply correlative, role for the N/C ratio in regulating cell growth and cell cycle progression. Expected final online publication date for the Annual Review of Genetics, Volume 56 is November 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Fungi play key roles in ecosystems and human societies as decomposers, nutrient cyclers, mutualists, and pathogens. Estimates suggest that roughly 3–13 million fungal species exist worldwide, yet considerable knowledge gaps exist regarding the mechanisms and consequences, both ecological and social, of fungal dispersal from local to global scales. In this review, we summarize concepts underlying fungal dispersal, review recent research, and explore how fungi possess unique characteristics that can broaden our understanding of general dispersal ecology. We highlight emerging frontiers in fungal dispersal research that integrate technological advances with trait-based ecology, movement ecology, social–ecological systems, and work in unexplored environments. Outstanding research questions across these themes are presented to stimulate theoretical and empirical research in fungal dispersal ecology. Advances in fungal dispersal will improve our understanding of fungal community assembly and biogeography across a range of spatial scales, with implications for ecosystem functioning, global food security, and human health. Expected final online publication date for the Annual Review of Ecology, Evolution, and Systematics, Volume 53 is November 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Extortion occurs when one person uses some combination of threats and promises to extract an unfair share of benefits from another. Although extortion is a pervasive feature of human interaction, it has received relatively little attention in psychological research. But, we argue, extortion is structured quite similarly to far better-studied “reciprocal” social behaviors, such as conditional cooperation and retributive punishment. All of these strategies function to elicit some desirable behavior from a social partner and do so by constructing conditional incentives. The main difference is that the desired behavioral response is an unfair or unjust allocation of resources during extortion, whereas it is typically assumed to be a fair or just distribution of resources in studies of reciprocal cooperation and punishment. Thus, we propose that a common set of psychological mechanisms may render these strategies successful. We know from prior work that prosocial forms of reciprocity often work best when implemented inflexibly and intuitively, rather than deliberatively. This both affords long-term commitment to the reciprocal strategy, and also signals this commitment to social partners. We argue that, for the same reasons, extortion is likely to depend largely upon inflexible, intuitive psychological processes. Several existing lines of circumstantial evidence support this conjecture.
We are more likely to judge agents as morally culpable after we learn they acted freely rather than under duress or coercion. Interestingly, the reverse is also true: Individuals are more likely to be judged to have acted freely after we learn that they committed a moral violation. Researchers have argued that morality affects judgments of force by making the alternative actions the agent could have done instead appear comparatively normal, which then increases the perceived availability of relevant alternative actions. Across five studies, we test the novel predictions of this account. We find that the degree to which participants view possible alternative actions as normal strongly predicts their perceptions that an agent acted freely. This pattern holds both for perceptions of the prescriptive normality of the alternatives (whether the actions are good) and descriptive normality of the alternatives (whether the actions are unusual). We also find that manipulating the prudential value of alternative actions or the degree to which alternatives adhere to social norms, has a similar effect to manipulating whether the actions or their alternatives violate moral norms. This pattern persists even when what is actually done is held constant, and these effects are explained by changes in the perceived normality of the alternatives. Together, these results suggest that across contexts, participants' force judgments depend not on the morality of the actual action taken, but on the normality of possible alternatives. More broadly, our results build on prior work that suggests a unifying role of normality and counterfactuals across many areas of high-level human cognition.
Background Neuromodulation of brain circuits important for affect, behavior, and cognition may decrease the symptomatology and functional impairment of military veterans suffering from posttraumatic stress disorder (PTSD). Cranial electrotherapy stimulation (CES) techniques, such as Alpha-Stim®, have demonstrated preliminary benefit for symptoms that commonly co-occur with PTSD, such as pain, anxiety, depression, and insomnia. However, CES has not yet been specifically tested as a treatment for PTSD. The objective of this open-label pilot study was to examine feasibility, safety, and preliminary efficacy of Alpha-Stim® for treatment of PTSD. Methods Open-label Alpha-Stim® was administered to nine veterans who were diagnosed with PTSD via structured interview (Clinician-Administered PTSD Scale for DSM-5 [CAPS-5]) and were taking at least one psychotropic medication. Treatment consisted of 20 CES sessions administered at home over 40 days. Effects on PTSD symptoms, functioning, depression symptoms, pain, anxiety symptoms, and insomnia were assessed at baseline and every week of treatment for four weeks. Effects on PTSD symptoms, depression symptoms, and pain were assessed one month and three months post-treatment. Results Seven patients (78%) successfully completed treatment. There were no adverse events. Following four weeks of Alpha-Stim® treatment, PTSD symptoms decreased by 38%, depression symptoms decreased by 52%, insomnia decreased by 34%, and pain decreased by 11%. Significant improvements in PTSD and depression, but not pain, persisted at one-month and three-months posttreatment. Presumptive loss of diagnosis rates (i.e., PTSD Checklist for DSM-5 total score below 33) immediately following treatment and one and three months later were 43%, 33%, and 29%, respectively. Conclusions Alpha-Stim® showed an excellent safety profile with no adverse effects. The results suggest preliminary efficacy for improving PTSD symptoms as well as concomitant depression symptoms, insomnia, and pain. Limitations of this pilot study include the open-label, uncontrolled design and small sample size. These results support additional larger, randomized controlled trials of Alpha-Stim® for veterans with PTSD.
China has the highest level of plastic production and consumption in the world. The plastic waste ban has resulted in a lack of raw materials for plastic reprocessing, while household appliance-related plastic (HAP), as a high-value and high-quality plastic waste source, receives great attention to fill such a gap. As HAP is scattered and has been rapidly increasing, a better understanding of the spatial-temporal patterns of HAP waste is critical. For the first time, this study quantifies the stocks and flows of plastics contained in five categories of household appliances (refrigerator, washing machine, air conditioner, TV, and computer) in China over 1978–2016 and maps their province-specific distribution through a dynamic stock-driven material flow analysis model. We find that (i) the HAP stocks are growing rapidly to reach around 25.4 million tonnes (MT) in 2016 and the HAP waste generated in 2016 is over 2 MT while the dismantling capacity is failing to catch up; (ii) the HAP waste in southeastern provinces is notably more than in northwestern provinces by approximately 11 times; (iii) washing machines (37%) and refrigerators (24%) are the major types of household appliances that contribute most to HAP waste generation; (iv) PP (38%) and PS (34%) are the major plastic types in HAP waste. These findings can provide quantitative references for the government to arrange waste management facilities, improve recycling capacities of dismantling companies, and promote coordinated efforts from multiple stakeholders to achieve efficient waste management of HAP.
Species ranges are forecast to change in response to warming temperatures and altered precipitation patterns, yet tree migration rates fail to track the pace of climate change. In anticipation of these changes, various forest adaptation management strategies have been broadly proposed, including intentionally modifying species composition via assisted migration of future climate adapted species. Despite the potential utility of these adaptation measures, practical evaluations are limited, particularly those applied to meet other ecological objectives such as supporting vulnerable, underrepresented, or degraded populations of foundational species. In this study, we examined the 4-year seedling survival and morpho-physiological response of American chestnut (Castanea dentata (Marsh.) Borkh.; n = 959 seeds sown), a functionally extirpated species. American chestnuts were grown within sixteen replicated 0.1 and 0.4 ha harvest gaps as part of a 160 ha co-developed (manager-scientist designed), operational-scale silvicultural trial (conditions of sufficient scope to be representative of commercial forest operations) in a northern-hardwood forest in the northeastern US. Chestnut restoration and migration potential (e.g., survival, absolute and relative growth rates, photosynthetic capacity) was assessed against the biophysical controls exerted on seedlings (e.g., understory competition, injury associated with browse and extreme cold winter temperatures) and in comparison to seedlings planted from eight other tree species (n = 480 planted per species) identified for assisted migration. Our results show the performance of American chestnut seedlings is controlled by the strength of local competition (odds of survival increased 2.6 times between four understory competition classes, p < 0.001) and cumulative winter shoot injury (relative growth in aboveground biomass adjusted for injury R2 = -0.85, p < 0.001) associated with cold intolerance likely linked to northward movement of chestnut seedlings transferred outside of their parental range. Still, the combined survival-growth response for American chestnuts ranked among the highest (2nd out of 6 possible rankings) relative to the other species tested, and even outperformed other comparable assisted migration species introduced from outside of their parental range. The implications of these findings highlight the potential for American chestnut plantings to be incorporated within both restoration and broader climate adaptation frameworks. Despite these promising outcomes, important biophysical (e.g., vegetative competition, harvest treatment, and variability in insulative snowpack) and climatic barriers for the reestablishment of this species remain. Given the paucity of reproductively viable American chestnuts or disease resistant breeding programs along northern range limits, this may generate a reliance on plant material obtained from outside of historically recognized safe transfer distances; however, increasingly shifting climate and species ranges may lead to better climate matches in the long term. Nevertheless, the broader applicability of this work illustrates the potential for cultural and ecological keystone species restoration efforts to be incorporated within climate adaptation frameworks to assist in the establishment of compositionally diverse and future climate-adapted forests.
We revisit the well-known negative association between unionization and workers’ job satisfaction in the United States, first identified over forty years ago. We find the association has disappeared since the Great Recession. The job satisfaction of both younger and older union workers in the National Longitudinal Surveys of 1979 and 1997 no longer differs compared to that of their non-union counterparts. When controlling for person fixed effects with panel data unionization is associated with greater job satisfaction throughout, suggesting that when one accounts for worker sorting into unionization, becoming unionized has always been associated with improvements in job satisfaction. We find a diminution in unions’ ability to lower quit rates which is consistent with declining union effectiveness as a ‘voice’ mechanism for unionized workers. We also find unions are able to minimize covered workers’ exposure to underemployment, a phenomenon that has increasingly negatively impacted non-union workers since the Great Recession.
In spite of overall improvements in air and water quality, biological stress from low pH and high concentrations of inorganic aluminum continue to impact fish and fish habitat in northeastern North America, with independent and interactive effects on individuals, populations and communities. Integrative indicators can therefore be useful in monitoring both impact and recovery across multiple scales. Using coupled water chemistry (pH, conductivity, and base cation and inorganic aluminum concentration), geographic (site elevation and watershed area) and biological (fish diversity, fish abundance, gill aluminum concentration and gill physiology) data, we developed an integrated indicator of acid-aluminum stress across the White and Green mountains in central New England, USA. As has been established in a number of previous studies, preliminary analysis clearly indicated that across all sites, inorganic aluminum concentration was consistently greatest during the spring season. Structural Equation modeling (SEM) revealed that toxic conditions (concurrent low pH and high concentrations of inorganic aluminum) were well summarized with an integrated toxicity score, related to both base cation concentrations and elevation, with sites at higher elevations more likely to experience toxic conditions as well as low base cation concentrations. Fish diversity and abundance generally trended negatively with toxicity score, with fewer cyprinids and sculpins at high toxicity score sites. In spite of considerable variation among individuals, gill aluminum was positively related to toxicity score for both Atlantic salmon and brook trout. Observed elevated gill aluminum levels associated with reduced gill metabolic activity in Atlantic salmon smolts from impacted systems likely result in impaired osmoregulatory function and seawater tolerance. Overall, our results suggest that the integrated toxicity score metric is associated with a syndrome of acute physiological stress, reduced abundance, and low species diversity for sensitive stream fishes in New England, and can likely serve as a reliable indicator of continued impairment or recovery of acid-aluminum vulnerable systems in this ecoregion.
The advent of Zero-Determinant (ZD) strategies has reshaped the study of reciprocity and cooperation in the iterated Prisoner's Dilemma games. The ramification of ZD strategies has been demonstrated through their ability to unilaterally enforce a linear relationship between their own average payoff and that of their co-player. Common practice conveniently represents this relationship by a straight line in the parametric plot of pairwise payoffs. Yet little attention has been paid to studying the actual geometry of the strategy space of all admissible ZD strategies. Here, our work offers intuitive geometric relationships between different classes of ZD strategies as well as nontrivial geometric interpretations of their specific parameterizations. Adaptive dynamics of ZD strategies further reveals the unforeseen connection between general ZD strategies and the so-called equalizers that can set any co-player's payoff to a fixed value. We show that the class of equalizers forming a hyperplane is the critical equilibrium manifold, only part of which is stable. The same hyperplane is also a separatrix of the cooperation-enhancing region where the optimum response is to increase cooperation for each of the four payoff outcomes. Our results shed light on the simple but elegant geometry of ZD strategies that is previously overlooked.
Lung cancer is a leading cause of death in both men and women globally. The recent development of tumor molecular profiling has opened opportunities for targeted therapies for lung adenocarcinoma (LUAD) patients. However, the lack of access to molecular profiling or cost and turnaround time associated with it could hinder oncologists' willingness to order frequent molecular tests, limiting potential benefits from precision medicine. In this study, we developed a weakly supervised deep learning model for predicting somatic mutations of LUAD patients based on formalin-fixed paraffin-embedded (FFPE) whole-slide images (WSIs) using LUAD subtypes-related histological features and recent advances in computer vision. Our study was performed on a total of 747 hematoxylin and eosin (H&E) stained FFPE LUAD WSIs and the genetic mutation data of 232 patients who were treated at Dartmouth-Hitchcock Medical Center (DHMC). We developed our convolutional neural network-based models to analyze whole slides and predict five major genetic mutations, i.e., BRAF, EGFR, KRAS, STK11, and TP53. We additionally used 111 cases from the LUAD dataset of the CPTAC-3 study for external validation. Our model achieved an AUROC of 0.799 (95% CI: 0.686–0.904) and 0.686 (95% CI: 0.620–0.752) for predicting EGFR genetic mutations on the DHMC and CPTAC-3 test sets, respectively. Predicting TP53 genetic mutations also showed promising outcomes. Our results demonstrated that H&E stained FFPE LUAD whole slides could be utilized to predict oncogene mutations, such as EGFR, indicating that somatic mutations could present subtle morphological characteristics in histology slides, where deep learning-based feature extractors can learn such latent information.
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4,380 members
Anita Tewari
  • Department of Microbiology and Immunology
Geoffrey Eglinton
  • Department of Earth Sciences (EARS)
Xun Shi
  • Department of Geography
Margaret Ackerman
  • Thayer School of Engineering
Robert Hill
  • Department of Biological Sciences
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