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•1.6% of hospitalized children below 5 years of age had a primary or any secondary discharge diagnosis of rotavirus.•Incidence of discharge diagnosis of rotavirus was 1071 and 542/100,000 person-years below 2 and 5 years of age, respectively.•A discharge diagnosis of rotavirus in children below 5 years of age likely under-reports true incidence by 1.59–2.02 times.•Adjusted and unadjusted incidence of rotavirus and all-cause gastroenteritis trended up, not down, from 1997 to 2011. Sentinel laboratory surveillance from one hospital and passive discharge diagnosis (Clinical Management System, CMS) data from all public Hospital Authority (HA) hospitals were used to estimate disease burden and incidence of rotavirus in hospitalised Hong Kong children over 14 rotavirus seasons (1 July 1997 to 31 March 2011). A primary diagnosis of a gastroenteritis-related disorder was noted in 9.8% of children aged below 5 years, and a primary or secondary diagnosis in 11.8%. Any CMS diagnosis of rotavirus (ICD 008.61) was initially used to derive incidence estimates of rotavirus by age group. Rotavirus was recorded as any primary or any secondary diagnosis in 1.6% of children below 5 years of age. The unadjusted incidence rates per 100,000 person-years based on any CMS diagnosis of rotavirus were: 249 (0 to <1m); 612 (1 to <2m); 1066 (2 to <6m); 1383 (6 to <11m); 959 (1 to <2y); 406 (2 to <3y); 233 (3 to <4y); 124 (4 to <5y). Overall the rotavirus incidence was 1071 in children below 2 years and 542 in children below 5 years of age, with the incidence rates trending up during the time period (p=0.001). A similar but less marked upward trend (p=0.046) was noted for the incidence of all-cause gastroenteritis. Laboratory results from a single surveillance hospital (1 July 2000 to 31 March 2011) were then linked to these CMS codes to derive adjustment factors for possible over- and under-diagnosis of rotavirus based on CMS codes alone. This analysis suggested that a CMS diagnosis of rotavirus alone likely under-reported true incidence by a factor of between 1.59 and 2.02 in children below 5 years of age. Despite the availability of rotavirus vaccines in the private sector since 2006, no reduction in the incidence of hospitalisation for either rotavirus or all-cause gastroenteritis was noted in Hong Kong children below 5 years of age over 14 rotavirus seasons (1997–2011).

About one-quarter of genetic variants that are associated with autism spectrum disorder (ASD) are due to de novo mutations in protein-coding genes. Brandler et al. wanted to determine whether changes in noncoding regions of the genome are associated with autism. They applied whole-genome sequencing to ∼2600 families with at least one affected child. Children with ASD had inherited structural variants in noncoding regions from their father. Regulatory regions of some specific genes were disrupted among multiple families, supporting the idea that a component of autism risk involves inherited noncoding variation. Science , this issue p. 327 Whole-genome sequencing identifies inherited noncoding variants in families affected by autism spectrum disorder. The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.

A copy number variant (CNV) of 16p11.2, which encompasses 30 genes, is associated with developmental and psychiatric disorders, head size and body mass. The genetic mechanisms that underlie these associations are not understood. To elucidate the effects of genes on development, we exploited the quantitative effects of CNV on craniofacial structure in humans and model organisms. We show that reciprocal deletion and duplication of 16p11.2 have characteristic mirror effects on craniofacial features that are conserved in human, rat and mouse. By testing gene dosage effects on the shape of the mandible in zebrafish, we show that the distribution of effects for all individual genes is consistent with that of the CNV, and some combinations have non-additive effects. Our results suggest that, at minimum, one third of genes within the 16p11.2 region influence craniofacial development, and the facial gestalt of each CNV represents a product of 30 dosage effects.

The genetic architecture of autism spectrum disorder (ASD) is known to consist of contributions from gene-disrupting de novo mutations and common variants of modest effect. We hypothesize that the unexplained heritability of ASD also includes rare inherited variants with intermediate effects. We investigated the genome-wide distribution and functional impact of structural variants (SVs) through whole genome analysis (>30X coverage) of 3,169 subjects from 829 families affected by ASD. Genes that are intolerant to inactivating variants in the exome aggregation consortium (ExAC) were depleted for SVs in parents, specifically within fetal-brain promoters, UTRs and exons. Rare paternally-inherited SVs that disrupt promoters or UTRs were over-transmitted to cases (P = 0.0013) and not to their typically-developing siblings. Protein-coding SVs were also associated with ASD (P = 0.0025). Recurrent functional noncoding deletions implicate the gene LEO1 in ASD. Our results establish that rare inherited SVs predispose children to ASD, with differing contributions from each parent.

Serum interleukin-8 (IL-8) levels and tumor neutrophil infiltration are associated with worse prognosis in advanced cancers. Here, using a large-scale retrospective analysis, we show that elevated baseline serum IL-8 levels are associated with poor outcome in patients ( n  = 1,344) with advanced cancers treated with nivolumab and/or ipilimumab, everolimus or docetaxel in phase 3 clinical trials, revealing the importance of assessing serum IL-8 levels in identifying unfavorable tumor immunobiology and as an independent biomarker in patients receiving immune-checkpoint inhibitors. In a retrospective analysis of data from four phase 3 clinical trials, elevated baseline serum IL-8 levels were associated with worse clinical outcomes in patients with multiple tumor types treated with anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combinatorial therapy.

I WOULD like to respond to a letter from \"Traveller\" (SCM Post, December 28) regarding our driver (Route I...

Inbred animals were historically chosen for genome analysis to circumvent assembly issues caused by haplotype variation but this resulted in a composite of the two genomes. Here we report a haplotype-aware scaffolding and polishing pipeline which was used to create haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle subspecies from contigs generated by the trio binning method. These assemblies reveal structural and copy number variants that differentiate the subspecies and that variant detection is sensitive to the specific reference genome chosen. Six genes with immune related functions have additional copies in the indicine compared with taurine lineage and an indicus-specific extra copy of fatty acid desaturase is under positive selection. The haplotyped genomes also enable transcripts to be phased to detect allele-specific expression. This work exemplifies the value of haplotype-resolved genomes to better explore evolutionary and functional variations. Taurine and indicine cattle have different desirable traits making them better adapted to different climates across the world. Here, Low et al. describe a pipeline to produce haplotype-resolved, chromosome-level genomes of Angus and Brahman cattle breeds from a crossbred individual and report on comparisons of the two genomes.

WE refer to the allegation headlined \"Upset by abusive driver\" (SCM Post, January 18) and wish to advise that an...

I WOULD like to respond to the complaint from Miss Alice Li (SCM Post, November 28) alleging reckless and inconsiderate driving on board...

In this study, once-daily treatment with oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients with genotype 1, 2, or 3 HCV infection, including those in whom previous therapy with telaprevir or boceprevir had failed. Chronic infection with hepatitis C virus (HCV) affects approximately 170 million people worldwide and is a major cause of cirrhosis and hepatocellular carcinoma. 1 , 2 HCV-related morbidity and mortality are increasing; since 2007, HCV-related deaths in the United States have exceeded those from human immunodeficiency virus (HIV) infection. 3 , 4 HCV is classified into six major genotypes. 5 , 6 Genotypes 1, 2, and 3 are found worldwide, with subtype 1a predominating in the United States and subtype 1b predominating in Europe, Japan, and China. 5 , 7 , 8 Peginterferon alfa–ribavirin treatment for chronic HCV infection is associated with a sustained virologic response (undetectable HCV RNA . . .