Differing patterns in intentional and unintentional poisonings among young people in England, 1998-2014: a population based cohort study

Background Accurate and up to date data on changes in poisoning incidence among young people are lacking. Recent linkage of UK primary care, hospital and mortality data allows these to be quantified to inform service delivery. Methods An open cohort study of 1 736 527 young people aged 10–24 between 1998 and 2014 was conducted using linked data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics deaths. Incidence rates (IRs) by poisoning intent were calculated by age, sex, deprivation and year. Results Total poisoning IRs increased by 25% from 1998/99 to 2013/14 [adjusted incidence rate ratio (aIRR) 1.25, 95% CI: 1.20–1.30]. Patterns differed markedly by intent. Intentional poisoning rates increased by 52% while unintentional rates remained unchanged. Intentional rates increased almost exclusively among females, gradually between 1998/99 and 2013/14 among 16–18 (88% increase) and 19–24 (36% increase) year olds but only increased among 10–15 year olds in the last 2 years (79% increase). A 2-fold increased risk of poisoning for the most compared to least deprived quintile existed (aIRR 2.21, 95% CI: 2.02–2.23) and remained over time. Conclusions Commissioning of primary and secondary prevention services needs to address the growing problem of intentional poisonings among young people

Assessing the potential of surface-immobilized molecular logic machines for integration with solid state technology

Molecular computation with DNA has great potential for low power, highly parallel information processing in a biological or biochemical context. However, significant challenges remain for the field of DNA computation. New technology is needed to allow multiplexed label-free readout and to enable regulation of molecular state without addition of new DNA strands. These capabilities could be provided by hybrid bioelectronic systems in which biomolecular computing is integrated with conventional electronics through immobilization of DNA machines on the surface of electronic circuitry. Here we present a quantitative experimental analysis of a surface-immobilized OR gate made from DNA and driven by strand displacement. The purpose of our work is to examine the performance of a simple representative surface-immobilized DNA logic machine, to provide valuable information for future work on hybrid bioelectronic systems involving DNA devices. We used a quartz crystal microbalance to examine a DNA monolayer containing approximately 5 × 10^{11} gates cm^{−2}, with an inter-gate separation of approximately 14 nm, and we found that the ensemble of gates took approximately 6 min to switch. The gates could be switched repeatedly, but the switching efficiency was significantly degraded on the second and subsequent cycles when the binding site for the input was near to the surface. Otherwise, the switching efficiency could be 80% or better, and the power dissipated by the ensemble of gates during switching was approximately 0.1 nW cm^{−2}, which is orders of magnitude less than the power dissipated during switching of an equivalent array of transistors. We propose an architecture for hybrid DNA-electronic systems in which information can be stored and processed, either in series or in parallel, by a combination of molecular machines and conventional electronics. In this architecture, information can flow freely and in both directions between the solution-phase and the underlying electronics via surface-immobilized DNA machines that provide the interface between the molecular and electronic domains

An experimental study of the putative mechanism of a synthetic autonomous rotary DNA nanomotor

DNA has been used to construct a wide variety of nanoscale molecular devices. Inspiration for such synthetic molecular machines is frequently drawn from protein motors, which are naturally occurring and ubiquitous. However, despite the fact that rotary motors such as ATP synthase and the bacterial flagellar motor play extremely important roles in nature, very few rotary devices have been constructed using DNA. This paper describes an experimental study of the putative mechanism of a rotary DNA nanomotor, which is based on strand displacement, the phenomenon that powers many synthetic linear DNA motors. Unlike other examples of rotary DNA machines, the device described here is designed to be capable of autonomous operation after it is triggered. The experimental results are consistent with operation of the motor as expected, and future work on an enhanced motor design may allow rotation to be observed at the single-molecule level. The rotary motor concept presented here has potential applications in molecular processing, DNA computing, biosensing and photonics

Opening the doors of possibility for gifted/high-ability children with learning difficulties: Preliminary assessment strategies for primary school teachers

The traits linked to gifted children with learning disabilities (twice-exceptional) are diverse and complex. Identification of these children can be hindered by a combination of factors, including variations in teacher knowledge and experience, inconsistencies in the visibility of high abilities coexisting simultaneously with one or more learning disabilities, and also the lack of a practical assessment tool. This mixed-methods study addresses the need for such a tool and other assessment strategies that primary school teachers can implement in the preliminary exploratory stage of identifying possible twice-exceptional children. In this process, the focus centres on learning strengths and difficulties. The first phase of the Study focused on procedures leading to the development and trialling of a comprehensive and useful teacher checklist questionnaire (TCQ). Its comprehensiveness was developed through reviewing research-based characteristics, anecdotal lists and teacher perceptions. Section A of the TCQ is based on the six natural-ability Domains found in Françoys Gagné's Differentiated Model of Giftedness and Talent (DMGT 2.0; 2008) or, more recently, his Expanded Model of Talent Development (EMTD, 2013). Section B has three familiar categories of learning difficulties known within the context of the primary school. In the trialling phase, ten teacher participants trialled the TCQ and ranked the selected children in their classes on every item in the nine categories. Overall, qualitative and quantitative analyses suggest promising trends in the preliminary investigation into the TCQ's internal reliability, validity and practical usefulness. In the second phase, six child participants were selected for case studies to determine whether other assessment strategies supported the findings of the TCQ. The results from Interviews with each child, a Parent/Teacher Questionnaire, a non-verbal intelligence test (Raven's Standard Progressive Matrices), and a Think-aloud protocol, affirm the worthiness of the TCQ, but variations in results suggest the importance of its inclusion as part of a comprehensive assessment protocol

Changes in poisonings among adolescents in the UK between 1992 and 2012: a population based cohort study

Background: Poisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK. Methods: A cohort study of 1 311 021 adolescents aged 10–17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation. Results: Overall poisoning incidence increased by 27% from the period 1992–1996 to 2007–2012, with the largest increases in intentional poisonings among females aged 16–17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992–1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007–2012) and alcohol related poisonings in females aged 15–16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007–2012). Conclusions: Adolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need

Poisoning substances taken by young people: a population-based cohort study

Background: Globally, poisonings account for most medically-attended self-harm. Recent data on poisoning substances are lacking, but needed to inform self-harm prevention. Aim: To assess poisoning substance patterns and trends among 10-24 year olds across England from 1998-2014. Design and Setting: Open cohort study of 1,736,527 young people using linked Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics mortality data. Method: Poisoning substances were identified by ICD-10 or Read codes. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substances by age, sex, index of multiple deprivation and year. Results: 40,333 poisoning episodes were identified, with 58% specifying the substances involved. The most common substances were paracetamol (39.8%), alcohol (32.7%), NSAIDs (11.6%), antidepressants (10.2%) and opioids (7.6%). Poisoning rates were highest at ages 16-18 for females, 19-24 for males. Opioid poisonings increased 5-fold from 1998-2014 (females: aIRR 5.30, 95%CI 4.08-6.89; males: 5.11, 95%CI 3.37-7.76), antidepressant poisonings 3 to 4-fold (females: aIRR 3.91, 3.18-4.80, males: 2.70, 2.04-3.58), aspirin/NSAID poisonings 3-fold (females: aIRR 2.84, 2.40-3.36, males: 2.76, 2.05-3.72) and paracetamol poisonings 3-fold in females (aIRR 2.87, 2.58-3.20). Across all substances poisoning incidence was higher in more disadvantaged groups, with the strongest gradient for opioid poisonings among males (aIRR 3.46, 2.24-5.36). Conclusion: It is important that GPs raise awareness with families of the substances young people use to self-harm, especially the common use of over-the-counter medications. Quantities of medication prescribed to young people at risk of self-harm and their families should be limited, particularly analgesics and antidepressants

Impact of the national home safety equipment scheme ‘Safe At Home’ on hospital admissions for unintentional injury in children under 5: a controlled interrupted time series analysis

Background: Unintentional home injuries are a leading cause of preventable death in young children. Safety education and equipment provision improve home safety practices, but their impact on injuries is less clear. Between 2009 and 2011 a national home safety equipment scheme was implemented in England (Safe At Home), targeting high injury rate areas and socio-economically disadvantaged families with children under 5. This provided a ‘natural experiment’ for evaluating the scheme’s impact on hospital admissions for unintentional injuries.Methods: Controlled interrupted time series analysis of unintentional injury hospital admission rates in small areas (Lower layer Super-Output Areas (LSOAs)) in England where the scheme was implemented (intervention areas, n=9,466)) matched with LSOAs in England and Wales where it was not implemented (control areas, n=9,466), with subgroup analyses by density of equipment provision.Results: 57,656 homes receiving safety equipment were included in the analysis. In the two years after the scheme ended, monthly admission rates declined in intervention areas (-0.33% (-0.47% to -0.18%)) but did not decline in control areas (0.04% (-0.11% to 0.19%), p value for difference in trend=0.001)). Greater reductions in admission rates were seen as equipment provision density increased. Effects were not maintained beyond two years after the scheme ended.Conclusions: A national home safety equipment scheme was associated with a reduction in injury-related hospital admissions in children under 5 in the 2-years after the scheme ended. Providing a higher number of items of safety equipment appears to be more effective in reducing injury rates than providing fewer items

Incident type 2 diabetes and risk of fracture: a comparative cohort analysis using UK primary care records

Objective: To estimate risk of fracture in men and women with recent diagnosis of type 2 diabetes compared to individuals without diabetes. Research Design and Methods: In this cohort study we used routinely-collected UK primary care data from The Health Improvement Network. In adults (>35 years) diagnosed with type 2 diabetes between 2004-2013 fractures sustained until 2019 were identified and compared to fractures sustained in individuals without diabetes. Multivariable models estimated time to first fracture following diagnosis of diabetes. Annual prevalence rates included at least one fracture in a given year. Results: Among 174,244 individuals with incident type 2 diabetes and 747,290 without diabetes, there was no increased risk of fracture among males with diabetes (adjusted hazards ratio (aHR) 0.97 (95%CI 0.94, 1.00)) and a small reduced risk among females (aHR 0.94, (95%CI 0.92, 0.96)). In those aged 85 years and over those in the diabetes cohort were at significantly lower risk of incident fracture (Males: aHR 0.85, 95%CI 0.71, 1.00; Females: aHR 0.85, 95%CI 0.78, 0.94). For those in the most deprived areas, aHRs were 0.90 (95%CI 0.83, 0.98) for males and 0.91 (95%CI 0.85, 0.97) for females. Annual fracture prevalence rates, by sex, were similar for those with and without type 2 diabetes.Conclusion: We found no evidence to suggest a higher risk of fracture following diagnosis of type 2 diabetes. After a diagnosis of type 2 diabetes individuals should be encouraged to make positive lifestyle changes, including undertaking weight-bearing physical activities that improve bone health

Towards a Bioelectronic Computer: A Theoretical Study of a Multi-Layer Biomolecular Computing System That Can Process Electronic Inputs

DNA molecular machines have great potential for use in computing systems. Since Adleman originally introduced the concept of DNA computing through his use of DNA strands to solve a Hamiltonian path problem, a range of DNA-based computing elements have been developed, including logic gates, neural networks, finite state machines (FSMs) and non-deterministic universal Turing machines. DNA molecular machines can be controlled using electrical signals and the state of DNA nanodevices can be measured using electrochemical means. However, to the best of our knowledge there has as yet been no demonstration of a fully integrated biomolecular computing system that has multiple levels of information processing capacity, can accept electronic inputs and is capable of independent operation. Here we address the question of how such a system could work. We present simulation results showing that such an integrated hybrid system could convert electrical impulses into biomolecular signals, perform logical operations and take a decision, storing its history. We also illustrate theoretically how the system might be able to control an autonomous robot navigating through a maze. Our results suggest that a system of the proposed type is technically possible but for practical applications significant advances would be required to increase its speed