AbstractSeed germination experiments are conducted in a wide variety of biological disciplines. Numerous methods of analysing the resulting data have been proposed, most of which fall into three classes: intuition-based germination indexes, classical non-linear regression analysis and time-to-event analysis (also known as survival analysis, failure-time analysis and reliability analysis). This paper briefly reviews all three of these classes, and argues that time-to-event analysis has important advantages over the other methods but has been underutilized to date. It also reviews in detail the types of time-to-event analysis that are most useful in analysing seed germination data with standard statistical software. These include non-parametric methods (life-table and Kaplan–Meier estimators, and various methods for comparing two or more groups of seeds) and semi-parametric methods (Cox proportional hazards model, which permits inclusion of categorical and quantitative covariates, and fixed and random effects). Each method is illustrated by applying it to a set of real germination data. Sample code for conducting these analyses with two standard statistical programs is also provided in the supplementary material available online (athttp://journals.cambridge.org/). The methods of time-to-event analysis reviewed here can be applied to many other types of biological data, such as seedling emergence times, flowering times, development times for eggs or embryos, and organism lifetimes.

After hematopoietic stem cell transplantation (HSCT), successful engraftment and immune recovery is necessary to protect the patient from relapse and infection. Many studies highlight the importance of conventional αβ T cell recovery after HSCT but the impact of γδ T cell recovery has not been well described. Here, we investigate the recovery of γδ T cells in 102 pediatric patients with acute leukemia in first clinical remission that underwent an allogeneic HSCT at St. Jude Children’s Research Hospital from 1996-2011. The mean age of the patients was 10.5 ± 5.9 years (range, 0.6-25.2) and the mean follow up of the survivors was 2.7±1.8 years (range 0.12-6.0). Diagnoses included 59% patients with ALL and 41% patients with AML. Multivariate analysis demonstrated significant impact of the maximum number of CD3+, CD4+ and CD8+ T cells and donor source on the γδ T cell recovery (P<0.0001, P<0.0001, P<0.0001 and P <0.004; respectively). Univariate and multivariate model found the number of γδ T cells after HSCT to be associated with infections (P = 0.026 and P = 0.02, respectively). We found the probability of infections for patients with an elevated number of γδ T cells was significantly lower compared to patients with low or normal γδ T cells after HSCT (18% vs. 54%; P=0.025). Bacterial infections were not observed in patients with elevated γδ T cells. Lastly, event free survival was significantly higher in patients with enhanced γδ T cell reconstitution compared to patients with low/normal γδ T cell reconstitution after HSCT (91% vs. 55%; P=0.04). Thus, γδ T cell may play an important role in immune reconstitution after HSCT.

Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2% ± 1.4%, 25.0% ± 1.3%, and 7.6% ± .8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P < .001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults.

Background The data on human rhinovirus (HRV), coronavirus (hCoV), bocavirus (hBoV), metapneumovirus (hMPV), Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis infections in children with cancer is limited. Methods We sought to determine prospectively the prevalence of respiratory pathogens in these children, using multiplexed-PCR. Results We enrolled 253 children with upper, or lower respiratory tract infection (URTI/LRTI) during a one year period. A respiratory virus was detected in 193 (76%) patients; 156 (81%) patients had URTI. Human rhinovirus was the most common virus detected in 97 (62%) and 24 (65%) patients with URTI and LRTI, respectively. Leukemia or lymphoma (LL) was the most common underlying diagnosis in 95 (49%) patients followed by solid tumor 47 (24%), post-hematopoietic stem cell transplant (HCT) 28 (15%), and brain tumor in 23 (12%) patients. By multiple logistic regression analysis hBoV was the most commonly detected respiratory virus in patients with LRTI (P = 0.008; odds ratio, 4.52; 95% confidence interval, 1.48-13.79). Co-infection with more than 1 virus was present in 47 (24%) patients, and did not increase the risk for LRTI. Two (0.7%) patients succumbed to LRTI from parainfluenza virus (PIV)-3 and respiratory syncytial virus/HRV infection, respectively. C.pneumoniae and M.pneumoniae were detected in 4 and 3 patients, respectively. Conclusions HRV was the most common virus detected in children with cancer and post-HCT hospitalized with an acute respiratory illness, and was not associated with increased morbidity. Prospective studies with viral load determination and asymptomatic controls are needed to study the association of these emerging respiratory viruses with LRTI in children with cancer and post-HCT.

Detection of respiratory viruses by molecular methods, in children without respiratory symptoms undergoing hematopoietic cell transplantation (HCT), has not been well described. A prospective study of 33 asymptomatic children detected respiratory viruses in 8 of 33 (24%) patients before HCT. Human rhinovirus (HRV) was detected in 5 patients, and human adenovirus (hADV) in 3 patients. Two additional patients shed HRV, and one shed human coronavirus (hCoV), post-HCT. Two patients had co-infections. Of the 11 asymptomatic patients where respiratory virus was detected, 3 (27%) later developed an upper respiratory tract infection, from the same virus.