Via Ca 2+ -imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, for each day the ensemble representation of this environment involved a unique subset of cells. Yet, cells within the ∼15-25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.CA1 place cells are considered crucial for spatial memory, but data is limited regarding whether their representations of space evolve over time scales of weeks or more 1 . Some theories suggest place cells should retain stable place fields for long-term retention of familiar environments 1 . Alternatively, dynamic aspects of place coding may facilitate distinct memory traces of different events occurring in the same environment 2 .Due to technical limitations, it has been only partially explored if CA1 representations of familiar environments are stable or evolve over time. Electrical recordings from many tens of cells are feasible 3 , but it is challenging to record from the same cells longer than a few days. Data on place fields' stability has largely been from small numbers of cells recorded over at most a week [4][5][6][7][8][9][10] . These studies have demonstrated cells with stable place fields, but the data have been too sparse to assess how coding evolves at the ensemble level.To study long-term coding dynamics, we combined (Fig. 1a): a viral vector (AAV2/5-CamKIIα-GCaMP3) to express the Ca 2+ -indicator GCaMP3 11 in pyramidal cells; a chronic mouse preparation for time-lapse imaging of CA1 over weeks 12 ; and a miniaturized (<2 g) microscope for Ca 2+ -imaging in hundreds of cells in freely behaving mice 13 . We thereby tracked somatic Ca 2+ dynamics of 515-1040 pyramidal cells in individual mice as they repeatedly visited a familiar track over 45 days.
Background: Gender stereotypes in science impede supportive environments for women. Research suggests that women's perceptions of these environments are influenced by stereotype threat (ST): anxiety faced in situations where one may be evaluated using negative stereotypes. This study developed and tested ST metrics for first time use with junior faculty in academic medicine. Methods: Under a 2012 National Institutes of Health Pathfinder Award, Stanford School of Medicine's Office of Diversity and Leadership, working with experienced clinicians, social scientists, and epidemiologists, developed and administered ST measures to a representative group of junior faculty. Results: 174 School of Medicine junior faculty were recruited (62% women, 38% men; 75% assistant professors, 25% instructors; 50% white, 40% Asian, 10% underrepresented minority). Women reported greater susceptibility to ST than did men across all items including ST vulnerability ( p < 0.001); rejection sensitivity ( p = 0.001); gender identification ( p < 0.001); perceptions of relative potential ( p = 0.048); and, sense of belonging ( p = 0.049). Results of career-related consequences of ST were more nuanced. Compared with men, women reported lower beliefs in advancement ( p = 0.021); however, they had similar career interest and identification, felt just as connected to colleagues, and were equally likely to pursue careers outside academia (all p > 0.42). Conclusions: Innovative ST metrics can provide a more complete picture of academic medical center environments. While junior women faculty are susceptible to ST, they may not yet experience all of its consequences in their early careers. As such, ST metrics offer a tool for evaluating institutional initiatives to increase supportive environments for women in academic medicine.
BackgroundSevere colitis flare from ulcerative colitis (UC) or Crohn’s disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis.MethodsA retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol.ResultsTwelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks.ConclusionWe report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.
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