Field studies were conducted in southern Ontario to determine the critical period of weed control in grain corn and the influence of weed interference on corn leaf area. The Gompertz and logistic equations were fitted to data representing increasing durations of weed control and weed interference, respectively. The beginning of the critical period varied from the 3- to 14-leaf stages of corn development However, the end of the critical period was less variable and ended on average at the 14-leaf stage. Weed interference reduced corn leaf area by reducing the expanded leaf area of each individual leaf and accelerating senescence of lower leaves. In addition, weed interference up to the 14-leaf stage of corn development impeded leaf expansion and emergence in 1989.

Correspondence n engl j med 375;5 nejm.org August 4, 2016 Human Coronavirus OC43 Associated with Fatal EncephalitisTo the Editor: Encephalitis is a serious neurologic syndrome characterized by brain inflammation that may be fatal. Although the majority of cases are caused by viruses, the identification of a causal organism can be difficult. Encephalopathy that affects patients with immunodeficiency is particularly challenging to diagnose, since the clinical presentation may be atypical and the differential diagnosis may include unusual pathogens or a noninfective cause. Deep sequencing of clinical samples has the potential to identify the pathogens associated with encephalitis, particularly in cases in which traditional techniques have not identified the candidate causative pathogen. 1Here we report the use of deep sequencing of a brain biopsy sample obtained from an 11-monthold boy with severe combined immunodeficiency who had symptoms of viral encephalitis with negative results on conventional diagnostic polymerase-chain-reaction (PCR) assay. The boy's family provided written informed consent.The boy underwent unconditioned cord-blood transplantation, which resulted in T-cell engraftment. Nonetheless, his condition continued to deteriorate, and he died 1.5 months after receiving the transplant. RNA sequencing of a brain biopsy sample obtained 2 months after the onset of symptoms showed the presence of human coronavirus OC43 (HCoV-OC43), which was sub- sequently confirmed on real-time PCR (threshold cycle, 24) and brain immunohistochemical analysis (Fig. 1). Full details on the case history, library preparation, bioinformatics analysis, species identification as reported by the profiling method metaMix, 2 PCR confirmation, immunohistochemical analysis, and phylogenetic and variant analyses are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.The human betacoronaviruses, including HCoV-OC43, are predominantly associated with respiratory tract infections. The group includes viruses that cause the severe acute respiratory syndrome and the Middle East respiratory syndrome. HCoV-OC43 is generally associated with mild upper respiratory tract infections, although it has been shown to have neuroinvasive properties. In vivo studies in mice have shown that HCoV-OC43 can infect neurons and cause encephalitis.3 The virus has also been shown to cause persistent infections in human neural-cell lines. 4 A single report identified HCoV-OC43 RNA in the cerebrospinal fluid of a child with acute disseminated encephalomyelitis. 5 In the case we describe here, three independent methods were used to identify HCoV-OC43 in brain tissue of a child with acute encephalomyelitis.Deep sequencing of biopsy material provides an important tool for the diagnosis of unexplained encephalomyelitis, particularly in patients with immunodeficiency who have undergone stem-cell transplantation, when the differential diagnosis may include immune-mediated inflammation or drug toxicity. The identificatio...

It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain–containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (–7), deletions of 7q (7q–), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with –7 and 7q– developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized.

Brain biopsy from a child with unknown cause of encephalopathy was deep-sequenced. Astrovirus VA1/HMO-C was identified, highly divergent from human astroviruses and 95% identical to astrovirus previously associated with encephalitis. Findings suggest astrovirus VA1/HMO-C is an under-recognized cause of viral encephalitis.