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For clinical trials with time‐to‐event as the primary endpoint, the clinical cutoff is often event‐driven and the log‐rank test is the most commonly used statistical method for evaluating treatment effect. However, this method relies on the proportional hazards assumption in that it has the maximal power in this circumstance. In certain disease areas or populations, some patients can be curable and never experience the events despite a long follow‐up. The event accumulation may dry out after a certain period of follow‐up and the treatment effect could be reflected as the combination of improvement of cure rate and the delay of events for those uncurable patients. Study power depends on both cure rate improvement and hazard reduction. In this paper, we illustrate these practical issues using simulation studies and explore sample size recommendations, alternative ways for clinical cutoffs, and efficient testing methods with the highest study power possible. [ABSTRACT FROM AUTHOR]

Study Objective: To compare surgical experience at myomectomy between patients with myomas pretreated with ulipristal acetate versus no pretreatment.Design: A prospective, observational, multicenter study of myomectomy procedures by any route (hysteroscopic, laparoscopic, or laparotomy) (Canadian Task Force classification II-2).Setting: Five university-affiliated hospitals including tertiary care and community sites.Patients: Any patient who underwent hysteroscopic, laparotomic, or laparoscopic myomectomy regardless of medical pretreatment.Interventions: Surgeons completed a Web-based questionnaire after each myomectomy procedure. Surgeons evaluated visualization, the myoma-myometrium relationship, extrusion, fluid deficit, blood loss, and overall ease of hysteroscopic myomectomies. For laparotomic/laparoscopic myomectomies, plane delineation, myoma separation, blood loss, and overall ease were assessed. The total surgical experience score was calculated by summing the values for each subscale.Measurements and Main Results: A total of 309 myomectomies were evaluated by 52 surgeons (response rate = 83%) at 5 institutions. Of 140 hysteroscopic myomectomies, 84 (60%) were performed without pretreatment, 29 (21%) after ulipristal acetate pretreatment, and 27 (19%) after pretreatment with gonadotropin-releasing hormone agonist/other. Of 169 laparotomic/laparoscopic myomectomies, 104 (62%) were performed without pretreatment, 46 (27%) after ulipristal acetate, and 19 (11%) after gonadotropin-releasing hormone agonist/other. The mean surgical experience score (±standard deviation) was comparable between the no pretreatment and ulipristal acetate groups for hysteroscopic myomectomies (13.8 ± 2.2 vs 13.3 ± 2.2, p = .35) and laparotomic/laparoscopic myomectomies (12.9 ± 4.1 vs 12.1 ± 4.2, p = .30). Compared with no pretreatment, more laparotomic/laparoscopic myomectomies after ulipristal acetate pretreatment were associated with difficult delineation of surgical planes (22 [47.8%] vs 23 [22.1%], p = .002) and difficult myoma separation (20 [43.5%] vs 21 [20.2%], p = .003). More myomas were described as soft with ulipristal acetate pretreatment (14 [30.4%] vs 17 [16.4%], p = .049). The rates of profuse/abundant endometrium during hysteroscopy were similar between the no pretreatment (21 [25.0%]) and ulipristal acetate (7 [24.1%], p = .93) groups.Conclusion: Despite differences in surgical nuances, the overall myomectomy experience was not negatively affected by ulipristal acetate pretreatment. [ABSTRACT FROM AUTHOR]

The article presents a discussion with experts on information literacy, who discuss information literacy in business and at workplace, including Elizabeth Malafi, coordinator of the Miller Business Center, Grace Liu, Stephane Goldstein, Executive Director at InformAll CIC. Topics include work order at public libraries, queries about career options and assistance to librarians, and decision making.

Background: The role of autonomic function in cognitive impairment is unclear. Heart rate variability (HRV) provides a feasible, non‐invasive measure of cardiac autonomic control. We examined whether HRV is associated with global cognition and cognitive impairment using 7‐day ambulatory ECG assessments in the Einstein Aging Study. Method: Analyses included 84 participants free of dementia (mean age 78.1 (± 5.2) years; 82% female; 39% non‐Hispanic White, 44% non‐Hispanic Black, mean education 14.7 (± 3.3 years)). Participants wore a small, single lead ECG device continuously over 7 days. Power spectral analyses were applied to determine HRV over 5‐minute epochs in the high (0.15‐0.40 Hz, hfHRV) and low (0.04‐0.15 Hz, lfHRV) frequency bands, and values were log transformed. Demographics, comorbidities, and cognition were assessed during clinic visits. Two tests per domain evaluated memory, executive function, language, visuo‐spatial and attention with impairment defined as performance ≥ 1.5 SD below the age, sex, education standardized norm on at least one test. Global cognition was assessed using the MoCA, and Mild Cognitive Impairment (MCI) was defined using Jak‐Bondi criteria. Associations of HRV with cognition were examined using logistic (MCI, domain specific impairment) and linear (MoCA) regression adjusting for age, sex, race/ethnicity and education, diabetes, and hypertension. Result: Mean MoCA score was 24 (SD 3.5), 21 (25%) had MCI and impairment was identified in 25% (memory), 28.6% (executive function), 21.4% (attention), 17.9% (language) and 27.4% (visuospatial). Both hfHRV and lfHRV were inversely associated with MCI (OR per 1 SD increase in log HRV: 0.47, p = 0.02 for hfHRV and 0.42, p = 0.01 for lfHRV) and with memory impairment (OR per 1 SD increase in log HRV: 0.52, p = 0.03 for hfHRV and 0.43, p = 0.01 for lfHRV). Higher hfHRV and lfHRV were each associated with better MoCA score (β for 1 SD increase in log HRV: 0.65, p = 0.046 for hfHRV; 0.80, p = 0.02). Conclusion: Whether HRV is associated with cognitive impairment remains unclear, particularly the role of hfHRV, indicative of parasympathetic control. Findings suggest that hfHRV is related to cognitive performance and impairment. Results for lfHRV also suggest joint effects of the sympathetic and parasympathetic systems. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization (2017) issued a call to improve health system performance through better coordination and integrated care. However, "the literature does not contain a one-size-fits-all model or process for successful integration, nor is there a firm empirical foundation for integration strategies and processes" (Suter et al., 2009). To implement effective inter-sectoral collaboration requires political will and innovative solutions to build communication across sectors to address local population needs (WHO, 2017). In 2017, 76 new cross-sectoral teams or "Tables" were created in Ontario (Canada) to address local population health needs. This provided a unique opportunity to conduct research to learn "how to" enable health systems integration and transformation through collaboration among diverse stakeholders. In this research, six "Tables" were studied; two were "Rural Tables", two were "Suburban Tables", and two were "Urban Tables") from 2018-2019. Aim/Objectives/Theories/Methods: The aim of this study was to understand the patterns of communication and collaboration among the participants of six "Tables". This research was innovative as it used both Relational Coordination and Complexity Theories in the context of health systems integration and transformation. The objectives were: 1)To identify key success factors/challenges to understand "how to" build cross-sectoral collaboration for leaders. 2)To develop a policy framework on "how to" build cross-sectoral collaboration for health systems integration/transformation for policymakers. A mixed-methods approach was used with Methodological Triangulation, which included quantitative surveys (at baseline and follow-up), qualitative interviews and member checking. Highlights/Results/Key Findings: The survey response rate was 62% at Baseline (n=45) and 25% at Follow-up (n=22). Relational Coordination Index Scores were "moderate" with no significant differences between Baseline and Follow-up and no differences between the stakeholders or "Tables". From the twelve interviews, it was discovered that context matters at the local levels. "Rural Tables" with "moderate" Relational Coordination reported "inter-dependency" and the "Suburban Tables" with "weak" Relational Coordination reported "inter-organizational challenges". The findings characterized the process of intentional cross-sectoral collaboration using both Relational Coordination and Complexity theories to understand the patterns of communication and collaboration among the stakeholders and the "Tables". This research was unique as the stakeholders collaborated voluntarily and were self-organized without any formal governance or structural changes, interventions, accountability targets or measurement of outcomes. This research adds a much-needed knowledge on cross-sectoral collaboration for leaders and policymakers in the development of self-organizing capacity supported by Relational Coordination. Conclusion: A policy framework on "how to" build cross-sectoral collaboration for health systems integration/transformation has been developed. The framework includes engaging with patients/families and key stakeholders, assessing relational coordination and structures, addressing health care as a complex adaptive system, and evaluation. Even though these proposed strategies are novel, further research is needed to drive health systems integration. Implications: In the literature, there is no one-size-fits-all model for health systems integration. Based on this conundrum, it is recommended that leaders view health care as a Complex Adaptive System; to allow the system to transform, change, and to develop inter-dependencies, interorganizational relationships and self-organizing capacities. Lessons learned from health systems integration in Canada are shared. [ABSTRACT FROM AUTHOR]

Study Objective: To compare surgical experience of laparoscopic/robotic myomectomy in premenopausal patients pretreated with ulipristal acetate (UPA) with women not hormonally pretreated.Design: A retrospective, multicenter cohort study of laparoscopic/robotic myomectomy procedure videos (Canadian Task Force Classification III).Setting: Multiple university-affiliated tertiary care hospitals.Patients: Fifty-five premenopausal women who underwent laparoscopic/robotic myomectomy for intramural myomas and were either pretreated with 3 months of UPA or had no hormonal pretreatment.Interventions: Laparoscopic/robotic myomectomy surgical videos were independently reviewed by 2 gynecologists blinded to whether or not patients received pretreatment with UPA. Each procedure was scored using a novel 22-point surgical global rating tool containing 6 subscales: depth of myometrial incision, ease of myoma-myometrium cleavage plane identification, ease of myoma detachment, blood loss during myoma detachment, myometrial blood loss after myoma detachment, and myoma consistency.Measurements and Main Results: Participating surgeons submitted 55 videos of laparoscopic/robotic myomectomy procedures recorded over a 3-year period (2012-2015). Fifty met the inclusion criteria (25 UPA-treated patients and 25 patients without hormonal pretreatment). Patients treated with UPA were more likely to be older than patients with no medical pretreatment (mean age = 33.5 vs 38.3 years, p = .002). There were no statistically significant differences regarding other baseline characteristics such as the largest diameter of myoma removed, the number of myomas removed, or the estimated blood loss. There was no difference in the physician assessors' mean global rating score for patients with UPA pretreatment versus no pretreatment (12.4 vs 13.4, p = .23). Within the 6 subscales, no differences were observed between the 2 groups. Each video was graded independently by 2 assessors, and there was high inter-rater agreement for the total score and each subscale.Conclusion: There was no difference in surgical experience for myomectomies of patients pretreated with UPA versus those without medical pretreatment. [ABSTRACT FROM AUTHOR]

Although various colorimetric methods have been actively developed for the detection of Ag+ ions because of their simplicity and reliability, the limits of detection of these methods are confined to the nanomolar (nM) level. Here, we demonstrate a novel strategy for colorimetric Ag+ detection with picomolar (pM) sensitivity. This strategy involves the use of poly(vinylpyrrolidone)- (PVP-) capped Pt nanocubes as artificial peroxidases that can effectively generate a colored signal by catalyzing the oxidation of peroxidase substrates. In the presence of Ag+ ions, the colored signal generated by these Pt cubes is greatly diminished because of the specific and efficient inhibition of Ag+ toward the peroxidase-like activity of the Pt cubes. This colorimetric method can achieve an ultralow detection limit of 80 pM and a wide dynamic range of 10-2- 104 nM. To the best of our knowledge, the method presented in this work shows the highest sensitivity for Ag+ detection among all reported colorimetric methods. Moreover, this method also features simplicity and rapidness as it can be conducted at room temperature, in aqueous solution, and requires only ~6 min. [ABSTRACT FROM AUTHOR]

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation. [ABSTRACT FROM AUTHOR]

To determine the difference in surgical complications for patients with a previous cesarean section (CS) undergoing abdominal, vaginal, or laparoscopic hysterectomy. A population-based retrospective cohort study. Province of Ontario, Canada. 10 300 patients with at least 1 CS between July 1, 1991, and February 17, 2018. Benign, nongravid hysterectomy between Apr 1, 2002, and March 31, 2018. The primary outcome was a composite of all surgical complications within 30 days of surgery. Secondary outcomes were rate of genitourinary complications, readmission to hospital, and emergency department visit occurring within 30 days of surgery. Of 10 300 patients who had at least one previous CS, who underwent subsequent hysterectomy for a benign indication, 7370 underwent an abdominal hysterectomy (71.55%), 813 (7.9%) had a vaginal hysterectomy, and 2117 (20.55%) underwent a laparoscopic hysterectomy. The adjusted odds of any surgical complication from hysterectomy was significantly lower when performed by the vaginal approach than the laparoscopic approach (odds ratio, 0.32; 95% confidence interval, 0.20–0.51; p <.0001). There was no difference in the odds of surgical complication between abdominal and laparoscopic approaches (odds ratio, 1.09; 95% confidence interval, 0.87–1.37; p =.45). Our retrospective population-based study demonstrates that, after previous CS, patients selected to undergo vaginal hysterectomy experienced lower risk than either abdominal or laparoscopic approaches. This suggests that CS alone should not be a contraindication to vaginal hysterectomy. [ABSTRACT FROM AUTHOR]