Cost-Effective Strategies for Mitigating a Future Influenza Pandemic with H1N1 2009 Characteristics

Background: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009–2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. Methodology/Principal Findings: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to$777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. Conclusion: The mild severity (low hospitalisation and case fatality rates) and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severit

Solidly Mounted Resonators with Carbon Nanotube Electrodes for Biosensing Applications

The work reported here shows a direct experimental comparison of the sensitivities of AlN solidly mounted resonators (SMR)-based biosensors fabricated with standard metal electrodes and with carbon nanotube electrodes. SMRs resonating at frequencies around 1.75 GHz have been fabricated, some devices using a thin film of multi-wall carbon nanotubes (CNTs) as the top electrode material and some identical devices using a chromium/gold electrode. Protein solutions with different concentrations were loaded on the top of the resonators and their responses to mass-load from physically adsorbed coatings were investigated. Results show that resonators using CNTs as the top electrode material exhibited higher frequency change for a given load due to the higher active surface area of a thin film of interconnecting CNTs compared to that of a metal thin film electrode and hence exhibited greater mass loading sensitivity. It is therefore concluded that the use of CNT electrodes on resonators for their use as gravimetric biosensors is viable and worthwhile

AlN-based BAW resonators with CNT electrodes for gravimetric biosensing

Solidly mounted resonators (SMRs) with a top carbon nanotubes (CNTs) surface coating that doubles as an electrode and as a sensing layer have been fabricated. The influence of the CNTs on the frequency response of the resonators was studied by direct comparison to identical devices with a top metallic electrode. It was found that the CNTs introduced significantly less mass load on the resonators and these devices exhibited a greater quality factor, Q (>2000, compared to ∼1000 for devices with metal electrodes), which increases the gravimetric sensitivity of the devices by allowing the tracking of smaller frequency shifts. Protein solutions with different concentrations were loaded on the top of the resonators and their responses to mass-load from physically adsorbed coatings were investigated. Results show that resonators using CNTs as the top electrode exhibited a higher frequency change for a given load (∼0.25 MHz cm2 ng−1) compared to that of a metal thin film electrode (∼0.14 MHz cm2 ng−1), due to the lower mass of the CNT electrodes and their higher active surface area compared to that of a thin film metal electrode. It is therefore concluded that the use of CNT electrodes on resonators for their use as gravimetric biosensors is a significant improvement over metallic electrodes that are normally employed

The relationship between sensory sensitivity and autistic traits in the general population.

Individuals with Autism Spectrum Disorders (ASDs) tend to have sensory processing difficulties (Baranek et al. in J Child Psychol Psychiatry 47:591–601, 2006). These difficulties include over- and under-responsiveness to sensory stimuli, and problems modulating sensory input (Ben-Sasson et al. in J Autism Dev Disorders 39:1–11, 2009). As those with ASD exist at the extreme end of a continuum of autistic traits that is also evident in the general population, we investigated the link between ASD and sensory sensitivity in the general population by administering two questionnaires online to 212 adult participants. Results showed a highly significant positive correlation (r = .775, p < .001) between number of autistic traits and the frequency of sensory processing problems. These data suggest a strong link between sensory processing and autistic traits in the general population, which in turn potentially implicates sensory processing problems in social interaction difficulties

The Impact of Case Diagnosis Coverage and Diagnosis Delays on the Effectiveness of Antiviral Strategies in Mitigating Pandemic Influenza A/H1N1 2009

BACKGROUND: Neuraminidase inhibitors were used to reduce the transmission of pandemic influenza A/H1N1 2009 at the early stages of the 2009/2010 pandemic. Policies for diagnosis of influenza for the purposes of antiviral intervention differed markedly between and within countries, leading to differences in the timing and scale of antiviral usage. METHODOLOGY/PRINCIPAL FINDINGS: The impact of the percentage of symptomatic infected individuals who were diagnosed, and of delays to diagnosis, for three antiviral intervention strategies (each with and without school closure) were determined using a simulation model of an Australian community. Epidemic characteristics were based on actual data from the A/H1N1 2009 pandemic including reproduction number, serial interval and age-specific infection rate profile. In the absence of intervention an illness attack rate (AR) of 24.5% was determined from an estimated R(0) of 1.5; this was reduced to 21%, 16.5% or 13% by treatment-only, treatment plus household prophylaxis, or treatment plus household plus extended prophylaxis antiviral interventions respectively, assuming that diagnosis occurred 24 hours after symptoms arose and that 50% of symptomatic cases were diagnosed. If diagnosis occurred without delay, ARs decreased to 17%, 12.2% or 8.8% respectively. If 90% of symptomatic cases were diagnosed (with a 24 hour delay), ARs decreased to 17.8%, 11.1% and 7.6%, respectively. CONCLUSION: The ability to rapidly diagnose symptomatic cases and to diagnose a high proportion of cases was shown to improve the effectiveness of all three antiviral strategies. For epidemics with R(0)< = 1.5 our results suggest that when the case diagnosis coverage exceeds ∼70% the size of the antiviral stockpile required to implement the extended prophylactic strategy decreases. The addition of at least four weeks of school closure was found to further reduce cumulative and peak attack rates and the size of the required antiviral stockpile

Analysis of the effectiveness of interventions used during the 2009 A/H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>Following the emergence of the A/H1N1 2009 influenza pandemic, public health interventions were activated to lessen its potential impact. Computer modelling and simulation can be used to determine the potential effectiveness of the social distancing and antiviral drug therapy interventions that were used at the early stages of the pandemic, providing guidance to public health policy makers as to intervention strategies in future pandemics involving a highly pathogenic influenza strain.</p> <p>Methods</p> <p>An individual-based model of a real community with a population of approximately 30,000 was used to determine the impact of alternative interventions strategies, including those used in the initial stages of the 2009 pandemic. Different interventions, namely school closure and antiviral strategies, were simulated in isolation and in combination to form different plausible scenarios. We simulated epidemics with reproduction numbers R₀of 1.5, which aligns with estimates in the range 1.4-1.6 determined from the initial outbreak in Mexico.</p> <p>Results</p> <p>School closure of 1 week was determined to have minimal effect on reducing overall illness attack rate. Antiviral drug treatment of 50% of symptomatic cases reduced the attack rate by 6.5%, from an unmitigated rate of 32.5% to 26%. Treatment of diagnosed individuals combined with additional household prophylaxis reduced the final attack rate to 19%. Further extension of prophylaxis to close contacts (in schools and workplaces) further reduced the overall attack rate to 13% and reduced the peak daily illness rate from 120 to 22 per 10,000 individuals. We determined the size of antiviral stockpile required; the ratio of the required number of antiviral courses to population was 13% for the treatment-only strategy, 25% for treatment and household prophylaxis and 40% for treatment, household and extended prophylaxis. Additional simulations suggest that coupling school closure with the antiviral strategies further reduces epidemic impact.</p> <p>Conclusions</p> <p>These results suggest that the aggressive use of antiviral drugs together with extended school closure may substantially slow the rate of influenza epidemic development. These strategies are more rigorous than those actually used during the early stages of the relatively mild 2009 pandemic, and are appropriate for future pandemics that have high morbidity and mortality rates.</p

Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications

Recently, piezoelectric thin films including zinc oxide (ZnO) and aluminium nitride (AlN) have found a broad range of lab-on-chip applications such as biosensing, particle/cell concentrating, sorting/patterning, pumping, mixing, nebulisation and jetting. Integrated acoustic wave sensing/microfluidic devices have been fabricated by depositing these piezoelectric films onto a number of substrates such as silicon, ceramics, diamond, quartz, glass, and more recently also polymer, metallic foils and bendable glass/silicon for making flexible devices. Such thin film acoustic wave devices have great potential for implementing integrated, disposable, or bendable/flexible lab-on-a-chip devices into various sensing and actuating applications. This paper discusses the recent development in engineering high performance piezoelectric thin films, and highlights the critical issues such as film deposition, MEMS processing techniques, control of deposition/processing parametres, film texture, doping, dispersion effects, film stress, multilayer design, electrode materials/ designs and substrate selections. Finally, advances in using thin film devices for lab-on-chip applications are summarised and future development trends are identified.The authors acknowledge support from the Innovative electronic Manufacturing Research Centre (IeMRC) through the EPSRC funded flagship project SMART MICROSYSTEMS (FS/01/02/10), Knowledge Transfer Partnership No KTP010548, EPSRC project EP/L026899/1, EP/F063865/1; EP/F06294X/1, EP/P018998/1, the Royal Society-Research Grant (RG090609) and Newton Mobility Grant (IE161019) through Royal Society and NFSC, the Scottish Sensing Systems Centre (S3C), Royal Society of Edinburgh, Carnegie Trust Funding, Royal Academy of Engineering-Research Exchange with China and India, UK Fluidic Network and Special Interest Group-Acoustofluidics, the EPSRC Engineering Instrument Pool. We also acknowledge the National Natural Science Foundation of China (Nos. 61274037, 51302173), the Zhejiang Province Natural Science Fund (No. Z11101168), the Fundamental Research Funds for the Central Universities (No. 2014QNA5002), EP/D03826X/1, EP/ C536630/1, GR/T24524/01, GR/S30573/01, GR/R36718/01, GR/L82090/01, BBSRC/E11140. ZXT acknowledges the supports from the National Natural Science Foundation of China (61178018) and the NSAF Joint Foundation of China (U1630126 and U1230124) and Ph.D. Funding Support Program of Education Ministry of China (20110185110007) and the NSAF Joint Foundation of China (Grant No. U1330103) and the National Natural Science Foundation of China (No. 11304209). NTN acknowledges support from Australian Research Council project LP150100153. This work was partially supported by the European Commission through the 6th FP MOBILIS and 7th FP RaptaDiag project HEALTH-304814 and by the COST Action IC1208 and by the Ministerio de Economía y Competitividad del Gobierno de España through projects MAT2010-18933 and MAT2013-45957R

Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008

<p>Abstract</p> <p>Background</p> <p>Data on complications in children with seasonal influenza virus infection are limited. We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU) with severe seasonal influenza.</p> <p>Methods</p> <p>From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED) including all paediatric hospitals in Germany. Cases to be reported were hospitalized children < 17 years of age with laboratory-confirmed influenza treated in a PICU or dying in hospital.</p> <p>Results</p> <p>Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008). The median age of the patients (12 males/8 females) was 7.5 years (range 0.1-15 years). None had received vaccination against influenza. In 14 (70%) patients, the infection had been caused by influenza A and in five (25%) by influenza B; in one child (5%) the influenza type was not reported. Patients spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation. Most frequent diagnoses were influenza-associated pneumonia (60%), bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary bacterial pneumonia (25%), and ARDS (25%). Eleven (55%) children had chronic underlying medical conditions, including 8 (40%) with chronic pulmonary diseases. Two influenza A- associated deaths were reported: <it>i) </it>an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, <it>ii) </it>a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure. For nine (45%) patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae).</p> <p>Conclusions</p> <p>Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany. The incidence of severe influenza cases in PICUs was relatively low. This may be either due to the weak to moderate seasonal influenza activity during the years 2005 to 2008 or due to under-diagnosis of influenza by physicians. Fifty% of the observed severe cases might have been prevented by following the recommendations for vaccination of risk groups in Germany.</p