A Predictive Spatial Model to Quantify the Risk of Air-Travel-Associated Dengue Importation into the United States and Europe

The number of travel-acquired dengue infections has been on a constant rise in the United States and Europe over the past decade. An increased volume of international passenger air traffic originating from regions with endemic dengue contributes to the increasing number of dengue cases. This paper reports results from a network-based regression model which uses international passenger travel volumes, travel distances, predictive species distribution models (for the vector species), and infection data to quantify the relative risk of importing travel-acquired dengue infections into the US and Europe from dengue-endemic regions. Given the necessary data, this model can be used to identify optimal locations (origin cities, destination airports, etc.) for dengue surveillance. The model can be extended to other geographical regions and vector-borne diseases, as well as other network-based processes

Prenatal exposure to multiple metallic and metalloid trace elements and the risk of bacterial sepsis in extremely low gestational age newborns: A prospective cohort study

Background Prenatal exposures to metallic and metalloid trace elements have been linked to altered immune function in animal studies, but few epidemiologic studies have investigated immunological effects in humans. We evaluated the risk of bacterial sepsis (an extreme immune response to bacterial infection) in relation to prenatal metal/metalloid exposures, individually and jointly, within a US-based cohort of infants born extremely preterm. Methods We analyzed data from 269 participants in the US-based ELGAN cohort, which enrolled infants delivered at <28 weeks' gestation (2002–2004). Concentrations of 8 trace elements—including 4 non-essential and 4 essential—were measured using inductively coupled plasma tandem mass spectrometry in umbilical cord tissue, reflecting in utero fetal exposures. The infants were followed from birth to postnatal day 28 with bacterial blood culture results reported weekly to detect sepsis. Discrete-time hazard and quantile g-computation models were fit to estimate associations for individual trace elements and their mixtures with sepsis incidence. Results Approximately 30% of the extremely preterm infants developed sepsis during the follow-up period (median follow-up: 2 weeks). After adjustment for potential confounders, no trace element was individually associated with sepsis risk. However, there was some evidence of a non-monotonic relationship for cadmium, with hazard ratios (HRs) for the second, third, and fourth (highest) quartiles being 1.13 (95% CI: 0.51–2.54), 1.94 (95% CI: 0.87–4.32), and 1.88 (95% CI: 0.90–3.93), respectively. The HRs for a quartile increase in concentrations of all 8 elements, all 4 non-essential elements, and all 4 essential elements were 0.92 (95% CI: 0.68–1.25), 1.19 (95% CI: 0.92–1.55), and 0.77 (95% CI: 0.57–1.06). Cadmium had the greatest positive contribution whereas arsenic, copper, and selenium had the greatest negative contributions to the mixture associations. Conclusions We found some evidence that greater prenatal exposure to cadmium was associated with an increased the risk of bacterial sepsis in extremely preterm infants. However, this risk was counteracted by a combination of arsenic, copper, and selenium. Future studies are needed to confirm these findings and to evaluate the potential for nutritional interventions to prevent sepsis in high-risk infants

Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor

Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in

EarLy Surveillance for Autoimmune diabetes - protocol for a qualitative study of general population and stakeholder perspectives on screening for type 1 diabetes in the UK [ELSA 1]

Objective Type 1 diabetes (T1D) is the most common form of diabetes in children, accounting for 96% of all diabetes, with 29,000 children affected in the UK. Studies have recently identified immunotherapies that safely delay the development of T1D for at least three years, and further therapies are in development. General population screening programmes in other countries can now accurately identify children with presymptomatic T1D who can be entered into prevention studies. The UK does not have such a system in place. We aim to explore whether parents and children in the UK would want to be part of such a programme of testing for T1D in the general population, how they would want to be informed and participate in such a programme, and how any barriers to recruitment and participation can be addressed. Additionally, the views of stakeholders who would be involved in the testing programme will be collected and analysed. Research Design and Methods We will interview parents/guardians and children aged 3-13 years about their views on screening for T1D. We will recruit purposefully to ensure representation across ethnicities and socioeconomic groups. Interviews will be transcribed, analysed, and used to inform iterative co-design work with additional families to address any issues raised. Similar qualitative work will be undertaken with professional stakeholders who would be involved in implementing any future screening programme. Where possible, all aspects of this study will be performed remotely by phone or online to minimise infection risk. Conclusions This qualitative study will provide the first insights into acceptability of testing and monitoring for T1D in the general population, from the perspective of families and stakeholders in the UK. Co-design work will help establish the barriers and identify strategies to mitigate and overcome these issues, as an important step towards consideration of national testing for T1D

The fallibility of memory in judicial processes: Lessons from the past and their modern consequences

The capability of adult and child witnesses to accurately recollect events from the past and provide reliable testimony has been hotly debated for more than one hundred years (Binet, 1900). Prominent legal cases of the 1980s and 1990s sparked lengthy debates and important research questions surrounding the fallibility and general reliability of memory. But what lessons have we learned, some forty years later, about the role of memory in the judicial system? In this review, we focus on what we now know about the consequences of the fallibility of memory for legal proceedings. We present a brief historical overview of false memories that focuses on three critical forensic areas that changed memory research: Children as eyewitnesses, historic sexual abuse, and eyewitness (mis)identification. We revisit some of the prominent trials of the 1980s and 1990s to not only consider the role false memories have played, but also to see how this has helped us understand memory today. Finally, we consider the way in which the research on memory (true and false) has been successfully integrated into some courtroom procedures

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and threematernally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins.We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such asmRNAexport, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in human

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin