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.

The interaction of human social behaviour and transmission is an intriguing aspect of the life cycle of respiratory viral infections. Although age-specific mixing patterns are often assumed to be the key drivers of the age-specific heterogeneity in transmission, the association between social contacts and biologically confirmed infection has not previously been tested at the individual level. We administered a questionnaire to participants in a longitudinal cohort survey of influenza in which infection was defined by longitudinal paired serology. Using a variety of statistical approaches, we found overwhelming support for the inclusion of individual age in addition to contact variables when explaining odds of infection: the best model not including age explained only 15.7% of the deviance, whereas the best model with age explained 23.6%. However, within age groups, we did observe an association between contacts, locations and infection: median numbers of contacts (or locations) reported by those infected were higher than those from the uninfected group in every age group other than the youngest. Further, we found some support for the retention of location and contact variables in addition to age in our regression models, with excess odds of infection of approximately 10% per additional 10 contacts or one location. These results suggest that, although the relationship between age and incidence of respiratory infection at the level of the individual is not driven by self-reported social contacts, risk within an age group may be.

Background A tailored immunization program is deemed more successful in encouraging vaccination. Understanding the profiles of vaccine hesitancy constructs in nurses can help policymakers in devising such programs. Encouraging vaccination in nurses is an important step in building public confidence in the upcoming COVID-19 and influenza vaccination campaigns. Objectives Using a person-centered approach, this study aimed to reveal the profiles of the 5C psychological constructs of vaccine hesitancy (confidence, complacency, constraints, calculation, and collective responsibility) among Hong Kong nurses. Design Cross-sectional online survey. Settings With the promotion of a professional nursing organization, we invited Hong Kong nurses to complete an online survey between mid-March and late April 2020 during the COVID-19 outbreak. Participants 1,193 eligible nurses (mean age = 40.82, SD = 10.49; with 90.0% being female) were included in the analyses. Methods In the online survey, we asked the invited nurses to report their demographics, COVID-19-related work demands (including the supply of personal protective equipment, work stress, and attitudes towards workplace infection control policies), the 5C vaccine hesitancy components, seasonal influenza vaccine uptake history, and the COVID-19 vaccine uptake intention. Latent profile analysis was employed to identify distinct vaccine hesitancy antecedent subgroups. Results Results revealed five profiles, including “believers” (31%; high confidence, collective responsibility; low complacency, constraint), “skeptics” (11%; opposite to the believers), “outsiders” (14%; low calculation, collective responsibility), “contradictors” (4%; high in all 5C constructs), and “middlers” (40%; middle in all 5C constructs). Believers were less educated, reported more long-term illnesses, greater work stress, higher perceived personal protective equipment sufficiency, and stronger trust in government than skeptics. They were older and had higher perceived personal protective equipment sufficiency than middlers. Also, believers were older and had greater work stress than outsiders. From the highest to the lowest on vaccination uptake and intention were believers and contradictors, then middlers and outsiders, and finally skeptics. Conclusion Different immunization programs can be devised based on the vaccine hesitancy profiles and their predictors. Despite both profiles being low in vaccination uptake and intention, our results distinguished between outsiders and skeptics regarding their different levels of information-seeking engagement. The profile structure reveals the possibilities in devising tailored interventions based on their 5C characteristics. The current data could serve as the reference for the identification of individual profile memb...

Patterns of social contact between individuals are important for the transmission of many pathogens and shaping patterns of immunity at the population scale. To refine our understanding of how human social behaviour may change over time, we conducted a longitudinal study of Hong Kong residents. We recorded the social contact patterns for 1450 individuals, up to four times each between May 2012 and September 2013. We found individuals made contact with an average of 12.5 people within 2.9 geographical locations, and spent an average estimated total duration of 9.1 h in contact with others during a day. Distributions of the number of contacts and locations in which contacts were made were not significantly different between study waves. Encounters were assortative by age, and the age mixing pattern was broadly consistent across study waves. Fitting regression models, we examined the association of contact rates (number of contacts, total duration of contact, number of locations) with covariates and calculated the inter- and intra-participant variation in contact rates. Participant age was significantly associated with the number of contacts made, the total duration of contact and the number of locations in which contact occurred, with children and parental-age adults having the highest rates of contact. The number of contacts and contact duration increased with the number of contact locations. Intra-individual variation in contact rate was consistently greater than inter-individual variation. Despite substantial individual-level variation, remarkable consistency was observed in contact mixing at the population scale. This suggests that aggregate measures of mixing behaviour derived from cross-sectional information may be appropriate for population-scale modelling purposes, and that if more detailed models of social interactions are required for improved public health modelling, further studies are needed to understand the social processes driving intra-individual variation.

The beneficial treatment effect associated with the addition of aflibercept to FOLFIRI was confirmed in Asian patients with pretreated metastatic colorectal cancer.