A Content Analysis of Common Relationship Challenges Among People Who Practice Polyamory

Approximately 1 out of 9 people in the U.S. have engaged in polyamory (Moors et al., 2021), a relationship type in which all involved agree to have multiple romantic and/or sexual partners. Despite the commonness of polyamory, there are many misconceptions about the polyamorous experience. However, research has yet to examine common challenges that people engaged in polyamory endure. The goal of the present qualitative study was to identify the disadvantages and stressors of polyamory in order to shed light on the unique experiences of people in these relationships. 219 adults who were currently in a polyamorous relationship were asked what are the disadvantages of polyamory and asked to report a maximum of five responses. The research team developed a codebook of 14 identified themes (e.g., jealousy, emotionally demanding type of relationship, stigma and negative evaluations, and health concerns). Two independent coders were trained on the codebook and iterative feedback was provided after the first 30 participants\u27 data were coded. After coding 763 responses with an inter-rater reliability of 78%, the top four challenges were identified. Time management issues were the most common challenge identified by participants, making up 21.1% of responses. Stigma, jealousy, and emotionally demanding type of relationship were also most commonly identified in the data. The goal of this study was to identify common disadvantages of engaging in a polyamorous relationship. The results of the present study will benefit mental health professionals who are attempting to treat and support individuals who engage in polyamory, as many of these challenges may be presenting concerns in a therapeutic setting. Additionally, people engaging in polyamory may receive validation and comfort knowing that they are not alone in these struggles

FARP1 Promotes the Dendritic Growth of Spinal Motor Neuron Subtypes through Transmembrane Semaphorin6A and PlexinA4 Signaling

SummaryThe dendritic morphology of neurons dictates their abilities to process and transmit information; however, the signaling pathways that regulate dendritic growth and complexity are poorly understood. Here, we show that retinoids induce the expression of the FERM Rho-GEF protein FARP1 in the developing spinal cord. FARP1 is expressed in subsets of motor neurons and is enriched in dendrites of lateral motor column (LMC) neurons that innervate the limb. FARP1 is necessary and sufficient to promote LMC dendritic growth but does not affect dendrite number or axonal morphology. We show that FARP1 serves as a specific effector of transmembrane Semaphorin6A and PlexinA4 signals to regulate LMC dendritic growth, and that its Rho-GEF domain is necessary for this function. These findings reveal that retinoid and Sema6A/PlexA4 signaling pathways intersect through FARP1 to control dendritic growth, and uncover the existence of subtype-specific signaling networks that control dendritic developmental programs in spinal motor neurons

A Branch-and-Price Algorithm for the Electric Autonomous Dial-A-Ride Problem

The Electric Autonomous Dial-A-Ride Problem (E-ADARP) consists in scheduling a fleet of electric autonomous vehicles to provide ride-sharing services for customers that specify their origins and destinations. The E-ADARP differs from the classical DARP in two aspects: (i) a weighted-sum objective that minimizes both total travel time and total excess user ride time; (ii) the employment of electric autonomous vehicles and a partial recharging policy. This paper presents a highly-efficient labeling algorithm, which is integrated into Branch-and-Price (B&P) algorithms to solve the E-ADARP. To handle (i), we introduce a fragment-based representation of paths. A novel approach is invoked to abstract fragments to arcs while ensuring excess-user-ride-time optimality. We then construct a new graph that preserves all feasible routes of the original graph by enumerating all feasible fragments, abstracting them to arcs, and connecting them with each other, depots, and recharging stations in a feasible way. On the new graph, partial recharging (ii) is tackled exactly by tailored Resource Extension Functions (REFs). We apply strong dominance rules and constant-time feasibility checks to compute the shortest paths efficiently. These methods construct the first labeling algorithm that can deal with minimizing (excess) user ride time. In the computational experiments, the B&P algorithm achieves optimality in 71 out of 84 instances. Remarkably, among these instances, 50 were solved optimally at the root node without branching. We identify 26 new best solutions, improve 30 previously reported lower bounds, and provide 17 new lower bounds for large-scale instances with up to 8 vehicles and 96 requests. In total 42 new best solutions are generated on previously solved and unsolved instances

The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos.

Ras-responsive element-binding protein 1 (Rreb1) is a zinc-finger transcription factor acting downstream of RAS signaling. Rreb1 has been implicated in cancer and Noonan-like RASopathies. However, little is known about its role in mammalian non-disease states. Here, we show that Rreb1 is essential for mouse embryonic development. Loss of Rreb1 led to a reduction in the expression of vasculogenic factors, cardiovascular defects, and embryonic lethality. During gastrulation, the absence of Rreb1 also resulted in the upregulation of cytoskeleton-associated genes, a change in the organization of F-ACTIN and adherens junctions within the pluripotent epiblast, and perturbed epithelial architecture. Moreover, Rreb1 mutant cells ectopically exited the epiblast epithelium through the underlying basement membrane, paralleling cell behaviors observed during metastasis. Thus, disentangling the function of Rreb1 in development should shed light on its role in cancer and other diseases involving loss of epithelial integrity

Beyond ChatBots: ExploreLLM for Structured Thoughts and Personalized Model Responses

Large language model (LLM) powered chatbots are primarily text-based today, and impose a large interactional cognitive load, especially for exploratory or sensemaking tasks such as planning a trip or learning about a new city. Because the interaction is textual, users have little scaffolding in the way of structure, informational "scent", or ability to specify high-level preferences or goals. We introduce ExploreLLM that allows users to structure thoughts, help explore different options, navigate through the choices and recommendations, and to more easily steer models to generate more personalized responses. We conduct a user study and show that users find it helpful to use ExploreLLM for exploratory or planning tasks, because it provides a useful schema-like structure to the task, and guides users in planning. The study also suggests that users can more easily personalize responses with high-level preferences with ExploreLLM. Together, ExploreLLM points to a future where users interact with LLMs beyond the form of chatbots, and instead designed to support complex user tasks with a tighter integration between natural language and graphical user interfaces.Comment: 19 pages, 11 figure

Low incidence of inflammatory bowel disease adverse events in adalimumab clinical trials across nine different diseases

OBJECTIVE: Adalimumab is approved for treatment of Crohn's disease and ulcerative colitis. Thus, we postulated that exacerbation or new-onset of inflammatory bowel disease (IBD) would be rare events in patients treated with adalimumab for non-IBD indications. This analysis evaluated the incidence of IBD adverse events (AEs) across adalimumab trials. METHODS: IBD AE rates in 75 adalimumab clinical trials in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, pediatric enthesitis-related arthritis, uveitis, hidradenitis suppurativa, adult and pediatric psoriasis, psoriatic arthritis, non-psoriatic arthritis peripheral spondyloarthritis (pSpA), axial spondyloarthritis (axSpA), including non-radiographic axSpA and ankylosing spondylitis, were analyzed. Search terms for IBD AEs (new onset or worsening/flare) included IBD, ulcerative colitis, Crohn's disease, and ulcerative proctitis. RESULTS: This analysis included 24,114 patients, representing 36,508 patient-years (PY) of adalimumab exposure. The overall rate (95% CI) of IBD AEs in adalimumab-treated patients was 0.1 (0.1-0.2)/100 PY (41 events), ranging from no events (psoriatic arthritis, uveitis, and pediatric trials) to 0.8 (0.2-2.2)/100 PY in pSpA; the rate of IBD in axSpA was 0.6 (0.4-1.0)/100 PY. During placebo-controlled trials, the overall IBD rate was 0.1 (0.0-0.3)/100 PY for adalimumab (3 events in 6781 patients; 2752 PY of exposure) and 0.1 (0.0-0.4)/100 PY for placebo (1 event in 3493 patients; 1246 PY of exposure) groups; IBD rates in axSpA were 0.5 (0.1-1.4)/100 PY and 0.6 (0.0-3.1)/100 PY, respectively. CONCLUSION: The rates of IBD AEs in adalimumab clinical trials were generally low across the evaluated diseases, including axSpA; all events occurred in adult patients

Neonatal hyperoxia promotes asthma-like features through IL-33–dependent ILC2 responses

Background Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and TH and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic TH responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity

The Evolution of Sunspot Magnetic Fields Associated with a Solar Flare

Solar flares occur due to the sudden release of energy stored in active-region magnetic fields. To date, the pre-cursors to flaring are still not fully understood, although there is evidence that flaring is related to changes in the topology or complexity of an active region's magnetic field. Here, the evolution of the magnetic field in active region NOAA 10953 was examined using Hinode/SOT-SP data, over a period of 12 hours leading up to and after a GOES B1.0 flare. A number of magnetic-field properties and low-order aspects of magnetic-field topology were extracted from two flux regions that exhibited increased Ca II H emission during the flare. Pre-flare increases in vertical field strength, vertical current density, and inclination angle of ~ 8degrees towards the vertical were observed in flux elements surrounding the primary sunspot. The vertical field strength and current density subsequently decreased in the post-flare state, with the inclination becoming more horizontal by ~7degrees. This behaviour of the field vector may provide a physical basis for future flare forecasting efforts.Comment: Accepted for Publication in Solar Physics. 16 pages, 4 figure

Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression

BACKGROUND:Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder caused most commonly by a defect in the NPC1 protein and characterized by widespread intracellular accumulation of unesterified cholesterol and glycosphingolipids (GSLs). While current treatment therapies are limited, a few drugs tested in Npc1(-/-) mice have shown partial benefit. During a combination treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ) and allopregnanolone, we noted increased lifespan for Npc1(-/-) mice receiving only 2-hydroxypropyl-beta-cyclodextrin (CD), the vehicle for allopregnanolone. This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit. METHODOLOGY/PRINCIPAL FINDINGS:Administration of CD to Npc1(-/-) mice beginning at either P7 or P21 and continuing every other day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as well as free sphingosine accumulation, reduced markers of neurodegeneration, and led to longer survival than any previous treatment regime. We reasoned that other lysosomal diseases characterized by cholesterol and GSL accumulation, including NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis (MPS) type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/-) mice showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or MPS IIIA failed to show reduction in storage. CONCLUSIONS/SIGNIFICANCE:Treatment with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1(-/-) and Npc2(-/-) mice. In contrast, CD failed to ameliorate cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA disease. Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis