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Decoupling Compression and Demixing: A Modular Penalized Matrix Decomposition Framework for Calcium and Voltage Imaging Data
No full textCalcium and voltage imaging produce high-dimensional fluorescence movies in which neural activity must be recovered from low-SNR measurements and is often obscured by structured backgrounds and acquisition artifacts. The objective is to recover and demix signals attributable to distinct sources. Most pipelines attempt this in a single stage; in practice, joint formulations are sensitive to initialization and hyperparameters and are computationally demanding. This thesis develops a modular alternative: perform compression and denoising first to obtain a compact, noise-reduced representation, and then demix on that representation.
First, the thesis introduces a patch-wise Penalized Matrix Decomposition (PMD) that constructs a structured, low-rank representation aligned with characteristics shared across modalities, without requiring modality-specific assumptions. Framing the initial stage as signal approximation rather than source separation yields robust compression and denoising without parameter tuning and compares favorably with standard dimensionality reduction baselines. This positions PMD as a general-purpose tool and a foundation from which to revisit the design of demixing.
Second, the thesis turns to demixing through targeted case studies, using the PMD representation as the substrate for redesigned, modality-adapted algorithms. Working directly in the compressed space improves conditioning, enables more stable and data-driven initialization, and reduces computational cost. These designs are translated into usable software and reproducible pipelines, and deployed in collaborative settings, illustrating how the modular framework supports scalable, routine analysis
Hippocampal Representations of Partner and Novel Individuals in Monogamous California Mice
No full textFor many species, having strong social bonds is essential for survival. Social bonds allow species to accomplish common goals, such as building a home and rearing offspring. However, it is not well understood what role social memory has in establishing and maintaining these bonds. Prior neurobiological studies of social memory have largely focused on Mus musculus, a promiscuous species that does not form lifelong pair bonds. Thus, it is unknown how monogamous species encode and recall social memory. The hippocampal region CA2 is critical for social memory, discriminating if a conspecific is novel or familiar, but its role in social bonding of monogamous species is unknown. In the rodent genus Peromyscus, closely related species display monogamous or promiscuous mating systems, making it an advantageous system to study the pair-bond. I sought to understand if monogamous versus promiscuous species store and retrieve memories differently.
To identify if mating systems impact social memory, I first compared social memory behaviors of promiscuous Peromyscus maniculatus with monogamous Peromyscus californicus and monogamous Peromyscus polionotus. To understand the social behavior of these mice, I employed four different behavioral assays: sociability, social novelty, five-trial social recognition, and a single stimulus pair-bond assay. I find that P. maniculatus and P. polionotus have no preference for either novel or littermate conspecifics but do demonstrate social memory in the five-trial social recognition tasks. In contrast, monogamous P. californicus has a strong preference for a littermate over a novel animal. P. polionotus and P. californicus both demonstrated selective pair-bond behaviors, suggesting that both monogamous species were able to recognize a pair-bonded partner. Results indicate species-specific and potentially sex-dependent mechanisms underlying the retrieval of established social memories.
To examine further how social memories are encoded, I sought to understand if CA2 participates in the memorization and recognition of a pair-bonded mate and how it computes this recognition in P. californicus (California mouse). To test this, I utilized 64-channel silicon probes to record from regions CA1 and CA2 of the hippocampus of freely behaving animals as they engaged in a social recognition task. Test mice were given the option to explore either its opposite-sex partner or an opposite-sex novel conspecific. Neural activity patterns differed across regions between social conditions as the pair-bond matured, with distinct populations of cells showing selective responses to partner versus novel conspecifics. At the completion of social recognition task, California mice were tested in a pair-bond task to assess pair-bond formation. When presented with a partner or novel mouse in a tether pair-bond option task, test mice prefer to display affiliative behavior towards partner mouse over novel. These findings help provide new insights into how pair-bond formation impacts the neural encoding of social information in the hippocampus
Climate change hopefulness, anxiety, and behavioral intentions among adolescents: randomized controlled trial of a brief “selfie” video intervention
No full textAim
We tested the utility of showing “selfie” videos to increase adolescents’ climate change hope, agency, and behavioral intentions, and to decrease their climate anxiety.
Methods We conducted a randomized controlled trial among healthy volunteers, ages 14 to 18, enrolled through a crowdsourcing platform. We randomly assigned participants (N = 1039) to view one of three 110-s-long video interventions featuring the same adolescent protagonist: positive (depicting an action-oriented stance); negative (defeatist stance); and control (neutral stance and unrelated content). The primary outcome was climate change hope; secondary outcomes were climate change anxiety, behavioral intention scales, and 100-point sliders about hopefulness and agency.
Results
Viewing positive “selfie” videos proved effective among adolescents in increasing hopefulness and a sense of agency regarding climate change (< 0.001), but not in decreasing climate anxiety or increasing intentions to engage in pro-environmental behaviors.
Conclusion
Brief video-based interventions featuring adolescent protagonists showed potential to increase hope and agency regarding climate change. While this single exposure did not directly affect anxiety levels or behavioral intentions, future research should examine whether repeated exposure and different "doses" of such interventions might influence these outcomes. The ubiquity and reach of social media hold promise to scale these inexpensive and specifically tailored interventions
Because of her, I am, I want, and I will be: An Exploratory Investigation of Black Mother-daughter Relationships across the Lifecourse
No full textThe Black family remains a poorly studied and understudied entity within scientific research. Notably, the roles of Black mothers and processes of Black mother-daughter relationships have not been given adequate scholarly attention. This study aimed to investigate the role and function of Black Mother-Daughter relationships in gendered racial socialization. Namely, this study focused on gendered race-based message transmission surrounding notions of Black womanhood, mental well-being, and hope and healing.
This research study included three research questions: 1) How do Black mothers and daughters describe and understand their mother-daughter relationship?, 2) How does the Black Mother-Daughter relationship change over time?, and 3) How do Black daughters perceive their mother's influence on the development of their general mental health and self-esteem?
This study used a qualitative inquiry that employed the Rigorous and Accelerated Data Reduction Analytic (RAdaR) technique to uncover the significant aspects of Black women’s gendered socialization in the family unit as well as the process by which messages of hope and healing are communicated. 18 Black mothers (N = 18) were interviewed regarding their experiences as Black mothers and daughters, including gendered racial socialization and mental health promotion within the family unit with a focus on transgenerational communication and gendered race-based messaging.
True to qualitative inquiry, this study did not anticipate any specific findings. However, the goal of the study was to center Black women’s familial experiences as related to their identity in hopes of informing future research, clinical practice, and policy. An analysis of 18 semi-structured interviews with Black mothers of Black daughters illustrated the participants’ experiences as Black women and girls within the family system particularly related to experiences of motherhood and daughterhood.
The data analysis revealed eight prominent themes related to Black women and girls’ gendered racial experiences related to the mother-daughter matrix: Yellow-Mothering, Gendered Racial Socialization, Grandmothering, Black matrescence, Family Environment, Gendered Racial Identity, Other Mothers and Auntie-ism, and Custody of the Inner Black Girl. Implications of the findings, study limitations, and future research recommendations are discussed
A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer
No full textAcross many solid tumor types, cancer-associated fibroblasts (CAFs) are abundant and highly heterogeneous, with distinct subpopulations exerting immunomodulatory functions. Though they have been well characterized in malignancies considered to be highly desmoplastic, how distinct CAF populations in lung adenocarcinoma (LUAD) influence the tumor–immune microenvironment is not well understood.
Here, we identify a novel population of immunomodulatory CAFs (imCAFs) in the LUAD tumor microenvironment, characterized by CHL1 expression and enriched in transcriptional programs involving immune regulation and chemokine signaling. Through single-cell and spatial transcriptomics, we demonstrate that imCAFs are spatially colocalized with CXCR3+ regulatory T (Treg) cells, a hyper-suppressive T cell subset that accumulates at the tumor border. Mechanistically, imCAFs produce CXCL9, a key chemoattractant that mediates the recruitment of CXCR3+ Treg cells to the tumor, promoting an immunosuppressive microenvironment. Functional profiling reveals that tumor-resident CXCR3+ Treg cells possess enhanced proliferative and suppressive capacity and are transcriptionally distinct from CXCR3- counterparts.
Genetic ablation of Cxcr3 in Treg cells or Cxcl9 in stromal cells significantly reduces Treg cell accumulation, resulting in enhanced CD8+ T cell activation and decreased tumor burden. Analogous CHL1+ imCAF-like fibroblasts are also observed in human NSCLC samples and were found to colocalize with Treg cells, with increased CHL1 expression in lung tumors being associated with reduced cytotoxicity scores and decreased progression-free survival. These findings uncover a critical stromal–immune axis wherein imCAF-derived CXCL9 orchestrates the localization and function of hyper-suppressive CXCR3+ Treg cells in LUAD and highlight the imCAF–CXCL9–CXCR3+ Treg cell recruitment circuit as a promising therapeutic target to restore anti-tumor immunity
Chromosomal instability as a driver of metastasis and cancer immune evasion in non-small cell lung cancer
No full textUp to 40% of all diagnosed brain metastases (BMs), a complication which portends an especially dismal prognosis despite recent therapeutic advances, originate from non-small cell lung cancers (NSCLC). NSCLCs which are characterized by co-occurring oncogenic KRAS and inactivating STK11 mutations, ~15% of all diagnosed cases, have an enhanced brain metastatic potential, and are particularly resistant to immune checkpoint blockade (ICB).
The salient biology of the treatment-naïve NSCLC BM ecosystem and tumor-intrinsic mechanisms by which STK11-mutant NSCLCs promote aggressive cancer behavior have both remained understudied. Here, we performed comprehensive, single nuclei RNA sequencing (snRNA-seq) coupled with whole genome sequencing to profile a cohort of NSCLC primary tumors (PTs) and BMs, validating our findings with extensive computational and matched patient tissue cohorts. We show that i) NSCLC BMs are enriched for computational and tissue surrogates of chromosomal instability (CIN) compared to PTs, ii) a pre-existing, CINhigh population which adopts neural-like features exists in NSCLC PTs and expands in BM samples, and iii), NSCLC BMs are characterized by a particularly immunosuppressive tumor microenvironment, altogether corroborating findings our group made in treatment-naïve melanoma BMs and in a pan-cancer BM analysis.
In our sequenced cohort, we found that tumors with STK11 mutation were particularly enriched for CIN. We experimentally confirmed this finding in vitro, showing that human and murine cancer cell lines with inactivating STK11-mutations, which encodes LKB1 protein, have higher rates of anaphase chromosome mis-segregation, and higher percentage of micronuclei formation than their LKB1-wild type counterparts. To facilitate the identification of putative CINhigh models, we developed an artificial-intelligence (AI) based tool, micronuclAI, to score cells grown in vitro for the presence of micronuclei. Through direct genetic modulation of CIN levels in LKB1-proficient and -deficient models, we show that CIN dictates type I IFN production in vitro and responses to ICB in vivo.
Additionally, we highlight that loss of LKB1 itself may promote CIN, with restoration of a functional allele leading to the rescue of immunogenic output and sensitivity to ICB. Finally, we show that functional relief of CIN through genetic knockout or pharmacological inhibition of cGAS, followed by re-engagement of STING, equilibrates the pathway towards its physiological function. Coupled with STING agonist or ICB therapy in vivo, cGAS-deficient tumors become overwhelmingly infiltrated by anti-tumor immune populations, leading to significant tumor eradication.
Overall, this work highlights cGAS inhibition in combination with ICB or STING agonists as an attractive therapeutic strategy for aggressive, chromosomally unstable NSCLC
Assessing decision-making capacity in clinical practice in Norway: a qualitative exploration of stakeholder perspectives
No full textBackground
Decision-making capacity (DMC) is a widely used criterion in health law, but assessments pose challenges in practice. In Norway, lacking DMC became an additional criterion for involuntary care and treatment following comprehensive amendments to the Mental Health Care Act in 2017. Contrary to the amendments’ objectives, involuntary care rates have continued to increase after an initial reduction in 2017. Assessing DMC typically involves four abilities: understanding, reasoning, appreciating relevant information, and communicating a choice. This four abilities model was introduced to aid in DMC assessments. With limited assessment experience pre-2017, the Norwegian context offers valuable insights into how stakeholders integrate DMC into clinical practice over time. This study aimed to explore how DMC was assessed in clinical practice following the introduction of a capacity-based mental health law governing involuntary care and treatment in Norway.
Methods
In 2018, semi-structured interviews and focus groups were conducted with 44 key stakeholders, including psychiatrists, specialists in clinical psychology, general practitioners, and lawyers in supervisory bodies (the Control Commission and County Governor). In 2022–23, 21 of these participants took part in individual follow-up interviews. The interviews were transcribed and thematically analysed.
Results
Data analysis generated three themes with subthemes: (1) DMC assessments primarily relied on the four abilities model in specialist care, experiencing gradual clinical adaptation with decreased importance, and exhibited variations in quality, particularly in primary care; (2) several challenges in DMC assessments, including lack of training in applying the four abilities model, ownership, continuity of care, information, and patient cooperation, with certain patient groups posing particular challenges, such as those with manic symptoms, substance misuse, and severe eating disorders; and (3) quality assurance measures needed, including systematic training and tools to improve assessment quality.
Conclusions
Assessing DMC involves variations and several challenges across the healthcare system. While the four abilities model served as a primary basis of DMC assessments in specialist care, systematic training, validated tools, and further research seem needed to improve assessment quality and better understand factors influencing assessments. Recognising the complex interplay between legal, health service, and societal factors when implementing health law reforms seems crucial for achieving their objectives
Traumatic events consequences on the Georgian internally displaced person’s mental health: an epidemiological national survey
No full textBackground
Georgia has experienced large waves of internal displacement and has one of the highest prevalence of internal displacement in the world, with IDPs representing about 7.5% of the population. Internal Displacement of Persons (IDP) carry multiple traumas that could affect the displaced populations.
Objective
To evaluate IDPs traumas and its mental health associations as compared to the non-displaced persons (non-IDPs) in Georgia.
Methods
This study employed a cross-sectional survey using representative sampling of IDPs and a randomized sample of non-IDPs totalling 1765 non-displaced people and 203 IDPs. Interviews were conducted face to face using ITQ (International Trauma Questionnaire) for PTSD, Composite Diagnostic Interview (CIDI) short form for anxious and depressive disorders, questions on suicidal behaviour; ASSIST for addictions, MH5 from SF36 for psychological distress. Results IDPs and non IDPs populations differed on many aspects: IDPs were older, retired, from rural areas with lower education than non IDPs. Exposure to multiple traumatic events was higher in IDPs: 22.08% reported 4 or more events versus 1.27% for non IDPs. IDPs had much higher PTSD impairing symptoms from ITQ than non-IDPs (8.59% versus 1.32%). They suffered more from psychological distress and anxiety disorders but have equal prevalence of depressive disorders and moderate or severe risk of addictions. IDPs have lower prevalence of suicidal thoughts than non IDPs. Once controlled for most of the sociodemographic factors, IDPs remained at very higher risk as compared to non-IDPs for PTSD symptoms with impairment (OR = 12.12, GAD OR = 3.38, and panic anxiety OR = 1.72).
Conclusions
Georgian IDPs are more likely to suffer from PTSD and anxious disorders than non-IDPs. Special attention should be paid to the population experiencing internally displacement securing their surrounding and providing psychosocial support
Facilitators and barriers of reducing sedentary behavior in sedentary and non-sedentary older adults: a descriptive qualitative study based on the COM-B model and TDF
No full textBackground
Prolonged sedentary behavior is a critical health risk for older adults. However, little is known about the distinct barriers and facilitators experienced by sedentary and non-sedentary older adults. Understanding these factors is essential for designing effective behavior change interventions.
Purpose
The study aims to identify and categorize the barriers and facilitators to reducing sedentary behavior among sedentary and non-sedentary older adults using the Capability, Opportunity, Motivation-Behavior (COM-B) model and Theoretical Domains Framework (TDF), thereby informing future mobile health (mHealth) interventions designed to reduce sedentary time in this population.
Methods
Data were collected through semi-structured interviews with older adults, conducted at two community hospitals in China between July 2024 and September 2024. The interviews focused on older adults’ psychological and physical capabilities, social and physical opportunities, and reflective and autonomous motivations related to sedentary behavior. According to the Canadian 24-Hour Movement Guidelines, participants were classified as sedentary (> 8 h/day sitting time) or non-sedentary (≤ 8 h/day) based on a participant characteristics questionnaire with verbal confirmation during the interview. The data were analyzed thematically, and the identified themes were mapped onto the COM-B model and TDF. Study procedures followed the COREQ checklist for qualitative research reporting.
Results
The study included 29 older adults, comprising 19 sedentary (65.5%) and 10 non-sedentary (34.5%). The following ten higher-order themes were identified: Lack of Knowledge (and Limited Knowledge); Lack of Methods (and Available Methods); Sedentary Triggers (and Interruptions); Lack of Management (and Self-management); Lack of Social Support (and Available Social Support); Lack of Environmental Support (and Available Environment Support); Perceptions and Conflicts (and Importance and Effort); Lack of Confidence (and Confidence); Limited Belief (and Understanding Health Benefits); and Limited Motivation (and Sufficient Motivation).
Conclusion
Sedentary older adults face barriers such as low awareness of health risks, lack of regulation strategies, and insufficient social support, while non-sedentary older adults demonstrate higher confidence, better self-regulation, and engage in structured activities supported by cues such as mobile health reminders
Anticipating the Limits of Climate Adaptation: Evidence from U.S. Irrigation Adoption
No full textWill technology help us adapt to future climate conditions? We examine irrigation—an essential technology for adapting agriculture to climate change—and find a "hump-shaped" adoption pattern: irrigation use increases at mild dryness levels and declines under severe dryness despite increasing benefits and willingness to pay for irrigated land. We provide evidence that water scarcity, itself worsened by climate change, drives these dynamics by limiting the effectiveness of irrigation technologies and their adoption in the United States.
This "window of opportunity" pattern —where adaptation technologies are most effective under moderate climate change and lose effectiveness thereafter— holds true for many climate adaptation strategies. Incorporating this feature into a stylized macro-finance model yields diverging adaptation strategies at different levels of global warming: adaptation investment is high for moderate global warming and low for severe warming. Hence uncertainty about future climate discourages adaptation investment by making its returns uncertain. Our results highlight the benefits of commitment mechanisms that can reduce climate uncertainty as they encourage more proactive adaptation efforts