High Rates of Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection in People Who Inject Drugs: A Prospective Cohort Study

Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterisedcohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possiblereinfections were identified (confirmed reinfections were those genetically distinct from the previous infection andpossible reinfections were used to define instances where genetic differences between infections could not beassessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfectionwas 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that ofprimary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]:2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93,95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting.In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recentinjecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmedreinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03,p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection.Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneouslyclear.Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at highrates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks ofhepatitis C reinfection are required

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science.Link_to_subscribed_fulltex

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant