Using the bootstrap to establish statistical significance for relative validity comparisons among patient-reported outcome measures

BACKGROUND: Relative validity (RV), a ratio of ANOVA F-statistics, is often used to compare the validity of patient-reported outcome (PRO) measures. We used the bootstrap to establish the statistical significance of the RV and to identify key factors affecting its significance. METHODS: Based on responses from 453 chronic kidney disease (CKD) patients to 16 CKD-specific and generic PRO measures, RVs were computed to determine how well each measure discriminated across clinically-defined groups of patients compared to the most discriminating (reference) measure. Statistical significance of RV was quantified by the 95% bootstrap confidence interval. Simulations examined the effects of sample size, denominator F-statistic, correlation between comparator and reference measures, and number of bootstrap replicates. RESULTS: The statistical significance of the RV increased as the magnitude of denominator F-statistic increased or as the correlation between comparator and reference measures increased. A denominator F-statistic of 57 conveyed sufficient power (80%) to detect an RV of 0.6 for two measures correlated at r = 0.7. Larger denominator F-statistics or higher correlations provided greater power. Larger sample size with a fixed denominator F-statistic or more bootstrap replicates (beyond 500) had minimal impact. CONCLUSIONS: The bootstrap is valuable for establishing the statistical significance of RV estimates. A reasonably large denominator F-statistic (F \u3e 57) is required for adequate power when using the RV to compare the validity of measures with small or moderate correlations (r \u3c 0.7). Substantially greater power can be achieved when comparing measures of a very high correlation (r \u3e 0.9)

CamAPS FX hybrid closed-loop with ultra-rapid lispro compared with standard lispro in adults with type 1 diabetes: a double-blind, randomized, crossover study.

INTRODUCTION To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. MATERIALS AND METHODS In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean±SD: age 44.5±10.7, HbA1c 7.1±0.9% [54±10mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. CamAPS FX closed-loop system was used in both periods. RESULTS In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9 to 10mmol/L; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean±SD: 78.7±9.8% vs. 76.2±9.6%; mean difference 2.5 percentage points [95%CI 0.8 to 4.2]; p=0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9±0.8mmol/L vs. 8.1±0.9mmol/L; p=0.048). The proportion of time with sensor glucose <3.9mmol/L was similar between interventions (median [IQR] ultra-rapid lispro 2.3% [1.3-2.7%] vs. standard insulin lispro 2.1% [1.4-3.3%]; p=0.33). No severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes

Defining success in graduate school

[Response to Weiner OD (2014) How should we be selecting our graduate students. Mol Biol Cell 25:429–430. doi: 10.1091/mbc.E13-11-0646.

Stereodifferentiation in the formation and decay of the encounter complex in bimolecular electron transfer with photoactivated acceptors

Experimental evidence has been obtained for the involvement of encounter complexes between both enantiomers of a π,π* triplet excited ketone and a chiral phenol or indole. Determination of the pre-equilibrium constants (KEC) and the intrinsic decay rate constants (kd) indicates a significant stereodifferentiation in both steps of the quenching process.Perez Prieto, Julia, [email protected] ; Galian, Raquel Eugenia, [email protected] ; Morant Miñana, Maria Carmen, [email protected]

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story

BACKGROUND A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence

Time spent in hypoglycemia according to age and time-of-day: Observations during closed-loop insulin delivery.

OBJECTIVE We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age-group and time-of-day. METHODS We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9mmol/l. Eight weeks of data for 88 participants were analyzed. RESULTS Median time spent in hypoglycemia over the 24-hour period was highest in children and adolescents (4.4%; [IQR 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); p<0.001 for difference between age-groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age-groups. CONCLUSION Time in hypoglycemia was highest in the pediatric age-group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age-groups