The exposure-lag response of air temperature on daily COVID-19 incidence is unclear and there have been concerns regarding the robustness of previous studies. Here we present an analysis of high spatial and temporal resolution using the distributed lag non-linear modelling (DLNM) framework. Utilising nearly two years’ worth of data, we fit statistical models to twelve Italian cities to quantify the delayed effect of air temperature on daily COVID-19 incidence, accounting for several categories of potential confounders (meteorological, air quality and non-pharmaceutical interventions). Coefficients and covariance matrices for the temperature term were then synthesised using random effects meta-analysis to yield pooled estimates of the exposure-lag response with effects presented as the relative risk (RR) and cumulative RR (RR_cum). The cumulative exposure response curve was non-linear, with peak risk at 15.1 °C and declining risk at progressively lower and higher temperatures. The lowest RR_cum at 0.2 °C is 0.72 [0.56,0.91] times that of the highest risk. Due to this non-linearity, the shape of the lag response curve necessarily varied by temperature. This work suggests that on a given day, air temperature approximately 15 °C maximises the incidence of COVID-19, with the effects distributed in the subsequent ten days or more.

Background: Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of paediatric cancer deaths. Multiple genetic abnormalities have been identified as prognostically significant in neuroblastoma patients. Optical genome mapping (OGM) is a novel cytogenetic technique used to detect structural variants, which has not previously been tested in neuroblastoma. We used OGM to identify copy number and structural variants (SVs) in neuroblastoma which may have been missed by standard cytogenetic techniques. Methods: Five neuroblastoma cell lines (SH-SY5Y, NBLW, GI-ME-N, NB1691 and SK-N-BE2(C)) and two neuroblastoma tumours were analysed using OGM with the Bionano Saphyr^® instrument. The results were analysed using Bionano Access software and compared to previous genetic analyses including G-band karyotyping, FISH (fluorescent in situ hybridisation), single-nucleotide polymorphism (SNP) array and RNA fusion panels for cell lines, and SNP arrays and whole genome sequencing (WGS) for tumours. Results: OGM detected copy number abnormalities found using previous methods and provided estimates for absolute copy numbers of amplified genes. OGM identified novel SVs, including fusion genes in two cell lines of potential clinical significance. Conclusions: OGM can reliably detect clinically significant structural and copy number variations in a single test. OGM may prove to be more time- and cost-effective than current standard cytogenetic techniques for neuroblastoma.

PURPOSE: Intermediate-risk neuroblastoma patients older than 18 months, with non– MYCN amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. METHODS: We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival. RESULTS: Among 98 tumors, 9/98 (9.2%) had oncogene amplifications ( CDK4/MDM2/TERT coamplification (n = 1), CDK4/MDM2 coamplification (n = 4), CDK4 (n = 2), TERT (n = 1), and MYC (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; P < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; P < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] v 93.3% [95% CI, 81.5 to 100]; P < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% v 61.1% [95% CI, 50.3 to 74.3]; P < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] v 80.9% [95% CI, 71.8 to 91.3]; P < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS. CONCLUSION: Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.