Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia

Background: A number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders. Methods: Using an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective. Results: Under a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination. Conclusions: Our study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations. Keywords: Zika, Microcephaly, Vaccination, Agent-based modeling, Cost-effectivenessYork University Librarie

Friction in metal-on-metal total disc arthroplasty: effect of ball radius

Total Disc Arthroplasty (TDA) can be used to replace a degenerated intervertebral disc in the spine. There are different designs of prosthetic discs, but one of the most common is a ball-and-socket combination. Contact between the bearing surfaces can result in high frictional torque, which can then result in wear and implant loosening. This study was designed to determine the effects of ball radius on friction. Generic models of metal-on-metal TDA were manufactured with ball radii of 10, 12, 14 and 16 mm, with a radial clearance of 0.015 mm. A simulator was used to test each sample in flexion-extension, lateral bending and axial rotation at frequencies of 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75 and 2 Hz under loads of 50, 600, 1200 and 2000 N, in new born calf serum. Frictional torque was measured and Stribeck curves were plotted to illustrate the lubrication regime in each case. It was observed that implants with a smaller ball radius showed lower friction and showed boundary and mixed lubrication regimes, whereas implants with larger ball radius showed boundary lubrication only. This study suggests designing metal-on-metal TDAs with ball radius of 10 or 12 mm, in order to reduce wear and implant loosening

Nanoparticle transport modelling in saturated porous media

University of Technology, Sydney. Faculty of Engineering and Information Technology.This research deals with multi-scale descriptions of nano-colloidal transport in saturated porous media. Colloidal transport has been simulated, historically, by employing a pore-scale model. I argue that the use of such simulations on a continuum-scale where formulations are generally phenomenological, may be unsuitable if at all possible due to requirements for pore-scale parameterization. I propose to up-scale the pore-scale equation by inclusion of natural heterogeneity of porous media which consequently substitutes the pore-scale parameters (often unobtainable in real cases) with continuum-scale parameters (measurable at field). This approach transforms the pore-scale formulation into a Darcy-scale formulation, making it usable for real-world simulations. I demonstrate a closer agreement with experimental data once porous media’s natural heterogeneity is considered compared with the use of a mean value for media grain size in the conventional methods. These results can be explained by noting the fact that hydraulic conductivity of a porous medium is not controlled by the coarser or the median size grains. Rather, it is the smaller grains which ultimately determine (or in other words, restrict) the permeability of any given porous medium. By comparing various modelled scenarios, I also assess the magnitude of difference in predicted results which displays a significant divergence from the case where the porous medium is assumed to be homogeneous. Finally I aim to estimate the uncertainty associated with scenarios A (Yao’s equation) and B (Mehrabi_ Milne-Home equation) in the absence and presence of natural heterogeneity, respectively. The results showed a noticeable decrease of 9% to 87% in the uncertainty caused by the most prominent source of uncertainty in groundwater modelling; porous media’s heterogeneity. The uncertainty is generally lower closer to the contaminant release point and increases as the plume moves away from the source point. The more substantial improvements (reduction of uncertainty) was observed at selected point which were located further away from the release point. A framework for the assessment of nanoparticle transport in aquifers follows in which the extent of movement is estimated based on available field measured data and the probabilities of various potential realizations can be measured. This will help provide a much needed set of information for the policy-making processes with regards to new and emerging contaminants including engineered nanoparticles

Impact of viral drift on vaccination dynamics and patterns of seasonal influenza

BACKGROUND: Much research has been devoted to the determination of optimal vaccination strategies for seasonal influenza epidemics. However, less attention has been paid to whether this optimization can be achieved within the context of viral drift. METHODS: We developed a mathematical model that links different intra-seasonal dynamics of vaccination and infection to investigate the effect of viral drift on optimal vaccination for minimizing the total number of infections. The model was computationally implemented using a seasonal force of infection, with estimated parameters from the published literature. RESULTS: Simulation results show that the pattern of large seasonal epidemics is strongly correlated with the duration of specific cross-protection immunity induced by natural infection. Considering a random vaccination, our simulations suggest that the effect of vaccination on epidemic patterns is largely influenced by the duration of protection induced by strain-specific vaccination. We found that the protection efficacy (i.e., reduction of susceptibility to infection) of vaccine is a parameter that could influence these patterns, particularly when the duration of vaccine-induced cross-protection is lengthened. CONCLUSIONS: Given the uncertainty in the timing and nature of antigenically drifted variants, the findings highlight the difficulty in determining optimal vaccination dynamics for seasonal epidemics. Our study suggests that the short- and long-term impacts of vaccination on seasonal epidemics should be evaluated within the context of population-pathogen landscape for influenza evolution

Hydrochemical Effect of Different Quality of Water on the Behaviour of an Expansive Soil During Wetting and Drying Cycles

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The effect of quality of water on deformation, pH, EC (electrical conductivity) and osmotic suction was studied for an expansive soil during wetting and drying tests. The cyclic wetting and drying tests were conducted on samples of an expansive soil in a modified oedometer flooded with distilled, acidic and saline water. During the tests axial deformation of the samples was recorded continuously. pH and EC of pore water and reservoir water were measured through duplicated samples in a conventional oedometer. Osmotic suction was calculated based on the values of EC. The results show that the magnitude of deformation depends on the quality of the water and the deformation attained an equilibrium condition after almost four cycles. pH, EC and osmotic suction decreased with increasing suction. Copyright © 2016 John Wiley & Sons, Ltd

Observation of generalized optomechanical coupling and cooling on cavity resonance

Optomechanical coupling between a light field and the motion of a cavity mirror via radiation pressure plays an important role for the exploration of macroscopic quantum physics and for the detection of gravitational waves (GWs). It has been used to cool mechanical oscillators into their quantum ground states and has been considered to boost the sensitivity of GW detectors, e.g. via the optical spring effect. Here, we present the experimental characterization of generalized, that is, dispersive and dissipative optomechanical coupling, with a macroscopic (1.5mm)^2-sized silicon nitride (SiN) membrane in a cavity-enhanced Michelson-type interferometer. We report for the first time strong optomechanical cooling based on dissipative coupling, even on cavity resonance, in excellent agreement with theory. Our result will allow for new experimental regimes in macroscopic quantum physics and GW detection

Comparative dynamics of monovalent and bivalent vaccination for immunologically unrelated pathogens

Multivalent vaccines are designed to immunize against two or more pathogens in a single dose vaccination. A challenge for wide spread use of these vaccines is their lower protection efficacy compared to monovalent vaccines that immunize individuals against a single pathogen. We sought, for the first time, to evaluate the outcomes of bivalent and monovalent vaccines in terms of the reduction in the number of infections over time. For this evaluation, we developed epidemiological models governing the transmission dynamics of two immunologically unrelated pathogens, where immunity conferred by vaccination or natural infection of one pathogen does not provide any cross-protection against the other pathogen. We assumed that a monovalent vaccine provides full, but temporary, protection against a particular pathogen. While protecting against both pathogens requires two pathogen-specific monovalent vaccines, a single dose of the bivalent vaccine provides partial protection against both pathogens. We analyzed the two models to investigate the impact of vaccination. In addition to examining global behaviors and disease persistence of the models, we performed simulations to show the existence of a biologically feasible region for the bivalent vaccine to outperform monovalent vaccines for prevention of disease transmission using a lower number of vaccines

Diagnostic Accuracy of Chest Ultrasonography versus Chest Radiography for Identification of Pneumothorax: A Systematic Review and Meta-Analysis

Background: Early detection of pneumothorax is critically important. Several studies have shown that chest ultrasonography (CUS) is a highly sensitive and specific tool. The present systematic review and meta-analysis was designed to evaluate the diagnostic accuracy of CUS and chest radiography (CXR) for detection of pneumothorax. Materials and Methods: The literature search was conducted using PubMed, EMBASE, Cochrane, CINAHL, SUMSearch, Trip databases, and review article references. Eligible articles were defined as diagnostic studies on patients suspected for pneumothorax who underwent chest computed tomography (CT) scan and those assessing the screening role of CUS and CXR. Results: The analysis showed the pooled sensitivity and specificity of CUS were 0.87 (95% CI: 0.81-0.92; I2= 88.89, P<0.001) and 0.99 (95% CI: 0.98-0.99; I2= 86.46, P<0.001), respectively. The pooled sensitivity and specificity of CXR were 0.46 (95% CI: 0.36-0.56; I2= 85.34, P<0.001) and 1.0 (95% CI: 0.99-1.0; I2= 79.67, P<0.001), respectively. The Meta regression showed that the sensitivity (0.88; 95% CI: 0.82 - 0.94) and specificity (0.99; 95% CI: 0.98 - 1.00) of ultrasound performed by the emergency physician was higher than by non-emergency physician. Non-trauma setting was associated with higher pooled sensitivity (0.90; 95% CI: 0.83 – 0.98) and lower specificity (0.97; 95% CI: 0.95 – 0.99). Conclusion: The present meta-analysis showed that the diagnostic accuracy of CUS was higher than supine CXR for detection of pneumothorax. It seems that CUS is superior to CXR in detection of pneumothorax, even after adjusting for possible sources of heterogeneity. Key words: Pneumothorax; Ultrasonography; Radiography; Diagnostic tests, Routin

Abnormalities of mental rotation of hands associated with speed of information processing and executive function in chronic schizophrenic patients

Aim: Deficits in mental imagery ability have been reported in patients with schizophrenia. However, there is scarce evidence about the correlation between impairment in mental rotation and other cognitive deficits in the patients. The aim of this study was to assess mental rotation ability, along with other measures of cognitive function in patients with schizophrenia. Methods: The performance of 29 patients with schizophrenia was compared with 29 healthy controls. Mental rotation was measured with the Hand Rotation Task, and cognitive functions were measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Results: On Hand Rotation Task, the patients were significantly slower and less accurate compared to controls. Moreover, mental rotation accuracy was significantly correlated with all the BACS domains except verbal memory. In multiple regression analysis, the two BACS subscales, Tower of London and Symbol Coding tasks, were significant predictors and accounted for 41% of the variance in accuracy in the patients. Conclusion: These results support previous findings showing dysfunction of the posterior parietal cortex in schizophrenia, which is involved in general mental rotation, as well as other cognitive processes

The reliability and validity study of the Kinesthetic and Visual Imagery Questionnaire in individuals with Multiple Sclerosis

Motor imagery (MI) has been recently considered as an adjunct to physical rehabilitation in patients with multiple sclerosis (MS). It is necessary to assess MI abilities and benefts in patients with MS by using a reliable tool. The Kinesthetic and Visual Imagery Questionnaire (KVIQ) was recently developed to assess MI ability in patients with stroke and other disabilities. Considering the different underlying pathologies, the present study aimed to examine the validity and reliability of the KVIQ in MS patients. Method: Fifteen MS patients were assessed using the KVIQ in 2 sessions (5-14days apart) by the same examiner. In the second session, the participants also completed a revised MI questionnaire (MIQ-R) as the gold standard. Intra-class correlation coeffcients (ICCs) were measured to determine test-retest reliability. Spearman’s correlation analysis was performed to assess concurrent validity with the MIQ-R. Furthermore, the internal consistency (Cronbach’s alpha) and factorial structure of the KVIQ were studied. Results: The test-retest reliability for the KVIQ was good (ICCs: total KVIQ=0.89, visual KVIQ=0.85, and kinesthetic KVIQ=0.93), and the concurrent validity between the KVIQ and MIQ-R was good (r=0.79). The KVIQ had good internal consistency, with high Cronbach’s alpha (alpha=0.84). Factorial analysis showed the bi-factorial structure of the KVIQ, which was explained by visual=57.6% and kinesthetic=32.4%. Conclusions: The results of the present study revealed that the KVIQ is a valid and reliable tool for assessing MI in MS patients