Almost 1-2% of the human genome is located within 500 bp of either side of a transcription initiation site, whereas a far larger proportion (Ϸ25%) is potentially transcribable by elongating RNA polymerases. This observation raises the question of how the genome is packaged into chromatin to allow start sites to be recognized by the regulatory machinery at the same time as transcription initiation, but not elongation, is blocked in the 25% of intragenic DNA. We developed a chromatin scanning technique called ChAP, coupling the chromatin immunoprecipitation assay with arbitrarily primed PCR, which allows for the rapid and unbiased comparison of histone modification patterns within the eukaryotic nucleus. Methylated lysine 4 (K4) and acetylated K9͞14 of histone H3 were both highly localized to the 5 regions of transcriptionally active human genes but were greatly decreased downstream of the start sites. Our results suggest that the large transcribed regions of human genes are maintained in a deacetylated conformation in regions read by elongating polymerase. Common models depicting widespread histone acetylation and K4 methylation throughout the transcribed unit do not therefore apply to the majority of human genes.

The emergence and reemergence of coronavirus epidemics sparked renewed concerns from global epidemiology researchers and public health administrators. Mathematical models that represented how contact tracing and follow-up may control Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) transmissions were developed for evaluating different infection control interventions, estimating likely number of infections as well as facilitating understanding of their likely epidemiology. We reviewed mathematical models for contact tracing and follow-up control measures of SARS and MERS transmission. Model characteristics, epidemiological parameters and intervention parameters used in the mathematical models from seven studies were summarized. A major concern identified in future epidemics is whether public health administrators can collect all the required data for building epidemiological models in a short period of time during the early phase of an outbreak. Also, currently available models do not explicitly model constrained resources. We urge for closed-loop communication between public health administrators and modelling researchers to come up with guidelines to delineate the collection of the required data in the midst of an outbreak and the inclusion of additional logistical details in future similar models.

Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

Variability in the risk of transmission for respiratory pathogens can result from several factors, including the intrinsic properties of the pathogen, the immune state of the host and the host's behaviour. It has been proposed that self-reported social mixing patterns can explain the behavioural component of this variability, with simulated intervention studies based on these data used routinely to inform public health policy. However, in the absence of robust studies with biological endpoints for individuals, it is unclear how age and social behaviour contribute to infection risk. To examine how the structure and nature of social contacts influenced infection risk over the course of a single epidemic, we designed a flexible disease modelling framework: the population was divided into a series of increasingly detailed age and social contact classes, with the transmissibility of each age-contact class determined by the average contacts of that class. Fitting the models to serologically confirmed infection data from the 2009 Hong Kong influenza A/H1N1p pandemic, we found that an individual's risk of infection was influenced strongly by the average reported social mixing behaviour of their age group, rather than by their personal reported contacts. We also identified the resolution of social mixing that shaped transmission: epidemic dynamics were driven by intense contacts between children, a post-childhood drop in risky contacts and a subsequent rise in contacts for individuals aged 35–50. Our results demonstrate that self-reported social contact surveys can account for age-associated heterogeneity in the transmission of a respiratory pathogen in humans, and show robustly how these individual-level behaviours manifest themselves through assortative age groups. Our results suggest it is possible to profile the social structure of different populations and to use these aggregated data to predict their inherent transmission potential.