Considerations for study design in the DAHANCA 35 trial of protons versus photons for head and neck cancer

Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.</p

Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn’s disease

Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn’s disease, and a DMBT1−/− knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host–microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn’s disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn’s disease, and its severity, on three case–control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case–control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn’s disease, at least in Northern Europeans

Poverty in Nigeria

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Labor market transitions of immigrants with emphasis on marginalization and self-employment

Discrete competing risks, Panel data, Self-employment, C23, C41, J64,