Charge Transfer in Deoxyribonucleic Acid (DNA): Static Disorder, Dynamic Fluctuations and Complex Kinetic.

The fact that loosely bonded DNA bases could tolerate large structural fluctuations, form a dissipative environment for a charge traveling through the DNA. Nonlinear stochastic nature of structural fluctuations facilitates rich charge dynamics in DNA. We study the complex charge dynamics by solving a nonlinear, stochastic, coupled system of differential equations. Charge transfer between donor and acceptor in DNA occurs via different mechanisms depending on the distance between donor and acceptor. It changes from tunneling regime to a polaron assisted hopping regime depending on the donor-acceptor separation. Also we found that charge transport strongly depends on the feasibility of polaron formation. Hence it has complex dependence on temperature and charge-vibrations coupling strength. Mismatched base pairs, such as different conformations of the G・A mispair, cause only minor structural changes in the host DNA molecule, thereby making mispair recognition an arduous task. Electron transport in DNA that depends strongly on the hopping transfer integrals between the nearest base pairs, which in turn are affected by the presence of a mispair, might be an attractive approach in this regard. I report here on our investigations, via the I –V characteristics, of the effect of a mispair on the electrical properties of homogeneous and generic DNA molecules. The I –V characteristics of DNA were studied numerically within the double-stranded tight-binding model. The parameters of the tight-binding model, such as the transfer integrals and on-site energies, are determined from first-principles calculations. The changes in electrical current through the DNA chain due to the presence of a mispair depend on the conformation of the G・A mispair and are appreciable for DNA consisting of up to 90 base pairs. For homogeneous DNA sequences the current through DNA is suppressed and the strongest suppression is realized for the G(anti)・A(syn) conformation of the G・A mispair. For inhomogeneous (generic) DNA molecules, the mispair result can be either suppression or an enhancement of the current, depending on the type of mispairs and actual DNA sequence

Enhanced Safety Surveillance of Influenza Vaccines in General Practice, Winter 2015-16: Feasibility Study

BACKGROUND: The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced real-time surveillance of seasonal influenza vaccination. The EMA has specified a list of adverse events of interest to be monitored. The EMA sets out 3 different ways to conduct such surveillance: (1) active surveillance, (2) enhanced passive surveillance, or (3) electronic health record data mining (EHR-DM). English general practice (GP) is a suitable setting to implement enhanced passive surveillance and EHR-DM. OBJECTIVE: This study aimed to test the feasibility of conducting enhanced passive surveillance in GP using the yellow card scheme (adverse events of interest reporting cards) to determine if it has any advantages over EHR-DM alone. METHODS: A total of 9 GPs in England participated, of which 3 tested the feasibility of enhanced passive surveillance and the other 6 EHR-DM alone. The 3 that tested EPS provided patients with yellow (adverse events) cards for patients to report any adverse events. Data were extracted from all 9 GPs' EHRs between weeks 35 and 49 (08/24/2015 to 12/06/2015), the main period of influenza vaccination. We conducted weekly analysis and end-of-study analyses. RESULTS: Our GPs were largely distributed across England with a registered population of 81,040. In the week 49 report, 15,863/81,040 people (19.57% of the registered practice population) were vaccinated. In the EPS practices, staff managed to hand out the cards to 61.25% (4150/6776) of the vaccinees, and of these cards, 1.98% (82/4150) were returned to the GP offices. Adverse events of interests were reported by 113 /7223 people (1.56%) in the enhanced passive surveillance practices, compared with 322/8640 people (3.73%) in the EHR-DM practices. CONCLUSIONS: Overall, we demonstrated that GPs EHR-DM was an appropriate method of enhanced surveillance. However, the use of yellow cards, in enhanced passive surveillance practices, did not enhance the collection of adverse events of interests as demonstrated in this study. Their return rate was poor, data entry from them was not straightforward, and there were issues with data reconciliation. We concluded that customized cards prespecifying the EMA's adverse events of interests, combined with EHR-DM, were needed to maximize data collection. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2016-015469

Saving bones without risking brain—bisphosphonates and risk of stroke: matched case-control study

Introduction There is conflicting evidence on the link between bisphosphonates and stroke with studies variously showing increased, decreased or unchanged risk. We investigated the association between bisphosphonate treatment and the risk of stroke using a large routine clinical dataset. Methods We used a matched nested case-control study design analysing routinely collected electronic data from patients registered at primary care practices in England participating in the Royal College of General Practitioners Research and Surveillance Centre. Cases were patients aged 18 years or over, either living or dead, recorded as having had a stroke in the period 1st January 2005 to March 31st 2016. Each case was matched to one control according to age, sex, general practice attended and calendar time. Data were analysed using Stata, version 14.2. Conditional logistic regression was used to determine odds ratios for stroke according to bisphosphonate treatment and duration in cases compared with controls. We adjusted for disease risk groups, cardiovascular risk factors, treatments, smoking status, alcohol consumption, ethnicity , bisphosphonate types, fracture and socioeconomic status using IMD (Index of Multiple Deprivation). Results We included 31,414 cases of stroke with an equal number of matched controls. Overall, 83.2% of cases and controls were aged 65 years or older and there were similar proportions of females (51.5%) and males (48.5%). Bisphosphonate treatment was not associated with stroke after adjusting for the wide range of confounders considered (OR 0.86, 95% CI 0.62 - 1.19). Conclusions We found no association between bisphosphonate treatment and risk of stroke, after adjusting for other confounders

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom : 2014/15 end of season results

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case–control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: −29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway

Incidence of Lower Respiratory Tract Infections and Atopic Conditions in Boys and Young Male Adults: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2015-2016.

BACKGROUND: The Royal College of General Practitioners Research and Surveillance Centre comprises more than 150 general practices, with a combined population of more than 1.5 million, contributing to UK and European public health surveillance and research. OBJECTIVE: The aim of this paper was to report gender differences in the presentation of infectious and respiratory conditions in children and young adults. METHODS: Disease incidence data were used to test the hypothesis that boys up to puberty present more with lower respiratory tract infection (LRTI) and asthma. Incidence rates were reported for infectious conditions in children and young adults by gender. We controlled for ethnicity, deprivation, and consultation rates. We report odds ratios (OR) with 95% CI, P values, and probability of presenting. RESULTS: Boys presented more with LRTI, largely due to acute bronchitis. The OR of males consulting was greater across the youngest 3 age bands (OR 1.59, 95% CI 1.35-1.87; OR 1.13, 95% CI 1.05-1.21; OR 1.20, 95% CI 1.09-1.32). Allergic rhinitis and asthma had a higher OR of presenting in boys aged 5 to 14 years (OR 1.52, 95% CI 1.37-1.68; OR 1.31, 95% CI 1.17-1.48). Upper respiratory tract infection (URTI) and urinary tract infection (UTI) had lower odds of presenting in boys, especially those older than 15 years. The probability of presenting showed different patterns for LRTI, URTI, and atopic conditions. CONCLUSIONS: Boys younger than 15 years have greater odds of presenting with LRTI and atopic conditions, whereas girls may present more with URTI and UTI. These differences may provide insights into disease mechanisms and for health service planning

Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017.

BACKGROUND: Living in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this. OBJECTIVE: The objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments. METHODS: The population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs. RESULTS: For allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04). CONCLUSIONS: Those living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants

Near-Real Time Monitoring of Vaccine Uptake of Pregnant Women in a Primary Care Sentinel Network: Ontological Case Definition Across Heterogeneous Data Sources

Vaccination against influenza is important in pregnancy for the health of both mother and unborn baby. Influenza introduces risks to pregnancy and to the baby who relies on maternal antibodies for protection. Because the data associated with pregnancy is fragmented across multiple providers of health care, it is challenging to conduct pregnancy-related public health surveillance using a single data source. We report the integration of a novel ontological approach to identifying pregnancies in routine data with a web-based dashboard that feeds back information to general practices in a sentinel network. As a result, practices receive information about how well they are performing influenza vaccination in pregnancy in near-real-time

Uptake of a dashboard designed to give realtime feedback to a sentinel network about key data required for influenza vaccine effectiveness studies

Dashboards are technologies that bringing together a range of data sources for observational or analytical purposes. We have created a customised dashboard that includes all the key data elements required for monitoring flu vaccine effectiveness (FVE). This delivers a unique dashboard for each primary care provider (general practice) providing data to the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), one of the oldest European surveillance systems. These FVE studies use a test negative case control (TNCC) design. TNCC requires knowledge of practice denominator; vaccine exposure, and results of influenza virology swabs carried out to identify in an influenza-like-illness (ILI), a clinical diagnosis, really is influenza. The dashboard displays the denominator uploaded each week into the surveillance system, compared with the nationally known practice size (providing face-validity for the denominator); it identifies those exposed to the vaccine (by age group and risk category) and virology specimens taken and missed opportunities for surveillance (again by category). All sentinel practices can access in near real time (4 working days in areas) their rates of vaccine exposure and swabs conducted. Initial feedback is positive; 80% (32/40) practices responded positively

Enhanced passive surveillance of influenza vaccination in England, 2016-2017- an observational study using an adverse events reporting card

Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92-6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93-3.47] and 1.77% [1.42-2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs