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As treatment options for patients with rectal cancer evolve, patients with early-stage rectal cancer may have a treatment choice between surgery and a trial of nonoperative management. Patients must consider the treatments’ clinical tradeoffs alongside their personal goals and preferences. Shared decision-making (SDM) between patients and clinicians can improve decision quality when patients are faced with preference-sensitive care options. We interviewed 28 stakeholders (13 clinicians and 15 patients) to understand their perspectives on early-stage rectal cancer treatment decision-making. Clinicians included surgeons, medical oncologists, and radiation oncologists who treat rectal cancer. Adult patients included those diagnosed with early-stage rectal cancer in the past 5 years, recruited from an institutional database. A semi-structured interview guide was developed based on a well-established decision support framework and reviewed by the research team and stakeholders. Interviews were conducted between January 2022 and January 2023. Transcripts were coded by 2 raters and analyzed using thematic analysis. Both clinicians and patients recognized the importance of SDM to support high-quality decisions about the treatment of early-stage rectal cancer. Barriers to SDM included variable clinician motivation due to lack of training or perception of patients’ desires or abilities to engage, as well as time-constrained encounters. A decision aid could help facilitate SDM for early-stage rectal cancer by providing standardized, evidence-based information about treatment options that align with clinicians’ and patients’ decision needs.

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

Selective Immunoglobulin A Deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L).  Although the majority of people born with IgA deficiency lead normal lives without significant pathology, there is nonetheless a significant association of IgA deficiency with mucosal infection, increased risks of atopic disease, and a higher prevalence of autoimmune disease. To explain these phenomena, we have performed an extensive literature review to define the geoepidemiology of IgA deficiency and particularly the relative risks for developing Systemic Lupus Erythematosus, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, Crohn’s Disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and vitiligo; these diseases have strong data to support an association. We also note weaker associations with scleroderma, celiac disease, autoimmune hepatitis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia. Minimal if any associations are noted with myasthenia gravis, lichen planus, and multiple sclerosis. Finally, more recent data provide clues on the possible immunologic mechanisms that lead to the association of IgA deficiency and autoimmunity; these lessons are important for understanding the etiology of autoimmune disease.

Background & Aims: Primary biliary cholangitis (PBC) is a progressive‐cholestatic autoimmune liver disease. Dendritic cells (DC) are professional antigen‐presenting cells and their prominent presence around damaged bile ducts of PBC patients are documented. cDC1 is a rare subset of DC known for its cross‐presentation abilities and interleukin 12 production. Our aim was to assess the role of cDC1 in the pathogenesis of PBC. Methods: We utilized an inducible murine model of PBC and took advantage of the DC reporter mice Zbtb46gfp and the Batf3−/− mice that specifically lack the cDC1 subset. cDC1 cells were sorted from blood of PBC patients and healthy individuals and subjected to Bulk‐MARS‐seq transcriptome analysis. Results: Histopathology assessment demonstrated peri‐portal inflammation in wild type (WT) mice, whereas only minor abnormalities were observed in Batf3−/− mice. Flow cytometry analysis revealed a two‐fold reduction in hepatic CD8/CD4 T cells ratio in Batf3−/− mice, suggesting reduced intrahepatic CD8 T cells expansion. Histological evidence of portal fibrosis was detected only in the WT but not in Batf3−/− mice. This finding was supported by decreased expression levels of pro‐fibrotic genes in the livers of Batf3−/− mice. Transcriptome analysis of human cDC1, revealed 78 differentially expressed genes between PBC patients and controls. Genes related to antigen presentation, TNF and IFN signalling and mitochondrial dysfunction were significantly increased in cDC1 isolated from PBC patients. Conclusion: Our data illustrated the contribution the cDC1 subset in the pathogenesis of PBC and provides a novel direction for immune based cell‐specific targeted therapeutic approach in PBC. [ABSTRACT FROM AUTHOR]

Individuals that isolate themselves to give birth can use more than one strategy in choosing birth sites to maximize reproductive success. Previous research has focused on the consistency in the use of the same birth‐site across years (i.e., spatial fidelity), but individuals alternatively may use similar habitat conditions across years (i.e., habitat fidelity). Using GPS telemetry, we determined whether woodland caribou expressed spatial or habitat fidelity during calving, and evaluated intrinsic and extrinsic factors associated with expressing either type of fidelity. We identified 56 individuals with ≥2 putative birth events, via a movement‐based model, across northern Ontario between 2010 and 2014. Individuals were classified as expressing (1) spatial fidelity by comparing sequential calving locations to a random spatial distribution of available calving locations, (2) habitat fidelity using a logistic use model compared to a null (intercept only) model, (3) no fidelity (neither criterion met), or (4) both spatial and habitat fidelity (both criteria met). Across all individuals, 37% expressed no fidelity (36 of 98), 15% expressed only spatial fidelity (15 of 99), 35% expressed only habitat fidelity (34 of 98), and 14% expressed both spatial and habitat fidelity (14 of 98). Older individuals were more likely to express spatial fidelity, whereas lower availability of upland and lowland conifer forests without linear features increased the probability an individual expressed habitat fidelity. Our results indicate that managing for caribou calving needs to consider protecting both specific, known birthing sites, but also broad‐scale areas of preferred habitat for calving. Understanding the mechanisms that influence caribou expressing calving fidelity, and associated fitness costs, is crucial for the conservation of the species. [ABSTRACT FROM AUTHOR]

Migration is an adaptive life‐history strategy across taxa that helps individuals maximise fitness by obtaining forage and avoiding predation risk. The mechanisms driving migratory changes are poorly understood, and links between migratory behaviour, space use, and demographic consequences are rare.Here, we use a nearly 20‐year record of individual‐based monitoring of a large herbivore, elk (Cervus canadensis) to test hypotheses for changing patterns of migration in and adjacent to a large protected area in Banff National Park (BNP), Canada.We test whether bottom‐up (forage quality) or top‐down (predation risk) factors explained trends in (i) the proportion of individuals using 5 different migratory tactics, (ii) differences in survival rates of migratory tactics during migration and whilst on summer ranges, (iii) cause‐specific mortality by wolves and grizzly bears, and (iv) population abundance.We found dramatic shifts in migration consistent with behavioural plasticity in individual choice of annual migratory routes. Shifts were inconsistent with exposure to the bottom‐up benefits of migration. Instead, exposure to landscape gradients in predation risk caused by exploitation outside the protected area drove migratory shifts. Carnivore exploitation outside the protected area led to higher survival rates for female elk remaining resident or migrating outside the protected area.Cause‐specific mortality aligned with exposure to predation risk along migratory routes and summer ranges. Wolf predation risk was higher on migratory routes than summer ranges of montane‐migrant tactics, but wolf predation risk traded‐off with heightened risk from grizzly bears on summer ranges. A novel eastern migrant tactic emerged following a large forest fire that enhanced forage in an area with lower predation risk outside of the protected area.The changes in migratory behaviour translated to population abundance, where abundance of the montane‐migratory tactics declined over time. The presence of diverse migratory life histories maintained a higher total population abundance than would have been the case with only one migratory tactic in the population.Our study demonstrates the complex ways in which migratory populations change over time through behavioural plasticity and associated demographic consequences because of individuals balancing predation risk and forage trade‐offs. [ABSTRACT FROM AUTHOR]

Merrill etal. (1996) reported that persons with intellectual disability (ID) were slower at learning a visual search task to automaticity relative to persons of the same age without ID. For persons without ID, automaticity develops most rapidly under conditions in which a response is always the same for a particular stimulus. This study was designed to investigate whether persons with and without ID are differentially sensitive to the influence of consistently mapped versus inconsistently mapped stimulus responses. The primary manipulation was the consistency between a particular stimulus and the response to that stimulus in a visual search task. Sixteen participants with ID and 16 without ID searched displays of two, three, or four pictured objects to determine if a target was present. For half of the participants, the targets were always targets. For the other half, the targets became nontargets on 25% of the trials. Analyses focused on changes in response times associated with set size. Because automaticity allows for parallel processing, the elimination of significant effects of set size was taken as an index of the development of automaticity. Results indicated that inconsistent mapping significantly slowed the development of automaticity for the participants without ID but not for the participants with ID. Results were discussed in terms of the role of inhibition processes in the development of automatic search and detection. The effectiveness of inhibition processes was compromised by the consistency manipulation. The effect of the consistency manipulation was greater for the participants without ID because they were presumed to be using inhibition processes more effectively during practice than did the participants with ID.