267 research outputs found

    How to Compare Apples to Oranges Balancing Internal Candidates’ Job-performance Data with External Candidates’ Selection-test Results

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    It has been widely accepted that past performance is a good predictor of future performance. The exact strength of that relationship, however, has been unclear. Knowing the predictive power of past performance on future performance is particularly important for employers who make hiring decisions based in part on internal candidates’ performance record. Generally, some of the internal candidates’ performance would be measured at different points of time (e.g., 6 months, 12 months, and 24 months ago). Others under consideration will be external candidates, whose employment information is derived from selection devices such as structured interviews and intelligence tests. This paper uses a meta-analysis to examine 20 previously published studies on the stability of job performance over time. It provides an estimate of the relationship between existing performance measures and future performance, and models the nature of this relationship as a function of the elapsed time between measures. The findings show conclusively that, in general, past performance is, indeed, a good predictor of future performance for a variety of job types (i.e., exempt, nonexempt, and those that are evaluated subjectively). Using a hypothetical selection scenario, this report also demonstrates how that information can be used to compare multiple internal and external candidates

    Multicenter Validation of the Vasoactive-Ventilation-Renal Score as a Predictor of Prolonged Mechanical Ventilation After Neonatal Cardiac Surgery

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    Objectives: We sought to validate the Vasoactive-Ventilation-Renal score, a novel disease severity index, as a predictor of outcome in a multicenter cohort of neonates who underwent cardiac surgery. Design: Retrospective chart review. Setting: Seven tertiary-care referral centers. Patients: Neonates defined as age less than or equal to 30 days at the time of cardiac surgery. Interventions: Ventilation index, Vasoactive-Inotrope Score, serum lactate, and Vasoactive-Ventilation-Renal score were recorded for three postoperative time points: ICU admission, 6 hours, and 12 hours. Peak values, defined as the highest of the three measurements, were also noted. Vasoactive-Ventilation-Renal was calculated as follows: ventilation index + Vasoactive-Inotrope Score + Δ creatinine (change in creatinine from baseline × 10). Primary outcome was prolonged duration of mechanical ventilation, defined as greater than 96 hours. Receiver operative characteristic curves were generated, and abilities of variables to correctly classify prolonged duration of mechanical ventilation were compared using area under the curve values. Multivariable logistic regression modeling was also performed. Measurements and Main Results: We reviewed 275 neonates. Median age at surgery was 7 days (25th–75th percentile, 5–12 d), 86 (31%) had single ventricle anatomy, and 183 (67%) were classified as Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Category 4 or 5. Prolonged duration of mechanical ventilation occurred in 89 patients (32%). At each postoperative time point, the area under the curve for prolonged duration of mechanical ventilation was significantly greater for the Vasoactive-Ventilation-Renal score as compared to the ventilation index, Vasoactive-Inotrope Score, and serum lactate, with an area under the curve for peak Vasoactive-Ventilation-Renal score of 0.82 (95% CI, 0.77–0.88). On multivariable analysis, peak Vasoactive-Ventilation-Renal score was independently associated with prolonged duration of mechanical ventilation, odds ratio (per 1 unit increase): 1.08 (95% CI, 1.04–1.12). Conclusions: In this multicenter cohort of neonates who underwent cardiac surgery, the Vasoactive-Ventilation-Renal score was a reliable predictor of postoperative outcome and outperformed more traditional measures of disease complexity and severity

    Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: A phase 1 trial

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    Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies

    17: Impact of disease and mobilizing agents on initial and remobilization failure

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    Extubation Failure after Neonatal Cardiac Surgery: A Multicenter Analysis

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    Objectives To describe the epidemiology of extubation failure and identify risk factors for its occurrence in a multicenter population of neonates undergoing surgery for congenital heart disease. Study design We conducted a prospective observational study of neonates ≤30 days of age who underwent cardiac surgery at 7 centers within the US in 2015. Extubation failure was defined as reintubation within 72 hours of the first planned extubation. Risk factors were identified with the use of multivariable logistic regression analysis and reported as OR with 95% CIs. Multivariable logistic regression analysis was conducted to examine the relationship between extubation failure and worse clinical outcome, defined as hospital length of stay in the upper 25% or operative mortality. Results We enrolled 283 neonates, of whom 35 (12%) failed their first extubation at a median time of 7.5 hours (range 1-70 hours). In a multivariable model, use of uncuffed endotracheal tubes (OR 4.6; 95% CI 1.8-11.6) and open sternotomy of 4 days or more (OR 4.8; 95% CI 1.3-17.1) were associated independently with extubation failure. Accordingly, extubation failure was determined to be an independent risk factor for worse clinical outcome (OR 5.1; 95% CI 2-13). Conclusions In this multicenter cohort of neonates who underwent surgery for congenital heart disease, extubation failure occurred in 12% of cases and was associated independently with worse clinical outcome. Use of uncuffed endotracheal tubes and prolonged open sternotomy were identified as independent and potentially modifiable risk factors for the occurrence of this precarious complication

    Enhancer Sequence Variants and Transcription-Factor Deregulation Synergize to Construct Pathogenic Regulatory Circuits in B-Cell Lymphoma

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    SummaryMost B-cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions REs from normal GC B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression was deregulated in FL, targeted commandeered versus decommissioned REs. Our approach revealed two distinct subtypes of low-grade FL, whose pathogenic circuitries resembled GC B or activated B cells. FL-altered enhancers also were enriched for sequence variants, including somatic mutations, which disrupt transcription-factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC B-cell transformation
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