Coupled nanomechanical systems and their entangled eigenstates offer unique opportunities for the detection of ultrasmall masses. In this paper we show theoretically and experimentally that the stochastic and deterministic responses of a pair of coupled nanocantilevers provide different and complementary information about the added mass of an analyte and its location. This method allows the sensitive detection of minute quantities of mass even in the presence of large initial differences in the active masses of the two cantilevers. Finally, we show the fundamental limits in mass detection of this sensing paradigm.

BackgroundMany countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks.MethodsWe developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes.ResultsSwitching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively.ConclusionsThe switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

Rupture risk assessment of abdominal aortic aneurysms (AAA) by means of biomechanical analysis is a viable alternative to the traditional clinical practice of using a critical diameter for recommending elective repair. However, an accurate prediction of biomechanical parameters, such as mechanical stress, strain, and shear stress, is possible if the AAA models and boundary conditions are truly patient specific. In this work, we present a complete fluid-structure interaction (FSI) framework for patient-specific AAA passive mechanics assessment that utilizes individualized inflow and outflow boundary conditions. The purpose of the study is two-fold: (1) to develop a novel semiautomated methodology that derives velocity components from phase-contrast magnetic resonance images (PC-MRI) in the infrarenal aorta and successfully apply it as an inflow boundary condition for a patient-specific fully coupled FSI analysis and (2) to apply a one-way-coupled FSI analysis and test its efficiency compared to transient computational solid stress and fully coupled FSI analyses for the estimation of AAA biomechanical parameters. For a fully coupled FSI simulation, our results indicate that an inlet velocity profile modeled with three patient-specific velocity components and a velocity profile modeled with only the axial velocity component yield nearly identical maximum principal stress (σ1), maximum principal strain (ε1), and wall shear stress (WSS) distributions. An inlet Womersley velocity profile leads to a 5% difference in peak σ1, 3% in peak ε1, and 14% in peak WSS compared to the three-component inlet velocity profile in the fully coupled FSI analysis. The peak wall stress and strain were found to be in phase with the systolic inlet flow rate, therefore indicating the necessity to capture the patient-specific hemodynamics by means of FSI modeling. The proposed one-way-coupled FSI approach showed potential for reasonably accurate biomechanical assessment with less computational effort, leading to differences in peak σ1, ε1, and WSS of 14%, 4%, and 18%, respectively, compared to the axial component inlet velocity profile in the fully coupled FSI analysis. The transient computational solid stress approach yielded significantly higher differences in these parameters and is not recommended for accurate assessment of AAA wall passive mechanics. This work demonstrates the influence of the flow dynamics resulting from patient-specific inflow boundary conditions on AAA biomechanical assessment and describes methods to evaluate it through fully coupled and one-way-coupled fluid-structure interaction analysis.

The vibrations of microcantilevers in atomic force microscopes ͑AFMs͒ or radio frequency ͑RF͒ switches are strongly influenced by the viscous hydrodynamics of the surrounding fluid in the vicinity of a rigid wall. While prior efforts to model this hydrodynamic loading have focused on squeeze film damping effects at high Knudsen and squeeze numbers, the regimes of low Knudsen and squeeze numbers are also very important for which squeeze film models need to be discarded in favor of unsteady Stokes hydrodynamics. We extend the work of Green and Sader ͓Phys Fluids 17, 073102 ͑2005͒; J. Appl. Phys. 98, 114913 ͑2005͔͒ and present compact semianalytical formulas for the unsteady viscous hydrodynamic function of slender microbeams oscillating near rigid walls, in terms of key nondimensional numbers. Using these closed-form expressions, it becomes possible to predict easily the wet natural frequencies and quality factors of multiple modes of microcantilevers near rigid walls in diverse applications ranging from AFM in liquids to RF microswitches under ambient conditions. The semianalytical formulas are extensively validated by comparing their predicted wet natural frequencies and quality factors with those based on three-dimensional, transient flow-structure interaction simulations, as well as previous experiments performed in the field by other researchers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Olanzapine in an atypical antipsychotic agent which is associated with significant weight gain.• Metformin, an anti-hyperglycaemic agent, has been used to treat or prevent weight gain associated with olanzapine. • Meta-analyses on studies that have examined the use of metformin for treatment of antipsychotic-induced weight gain report significant heterogeneity. WHAT THIS STUDY ADDS• Systematic review and meta-analysis showed that metformin is useful for the short-term treatment of olanzapine-induced weight gain.Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n = 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P = 0.00002, I 2 = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m -2 lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand is currently considering) and a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations’ storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage.

Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent pneumococcal conjugate vaccine (PCV-7) to their National Immunization Programs (EPIs), these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients). We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1) the refrigerator space at the provincial district and sub-district levels and (2) the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm3/dose), all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L–1151 L per month) for the three largest formulations, and district level (range: 1 L–124 L per month) across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm3/dose), added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L–187 L, and district to sub-district levels ranged from 1 L–13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm3/dose) had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects on the availability of all vaccines that may not be initially apparent to decision-makers.

Abdominal aortic aneurysm (AAA) is a vascular condition where the use of a biomechanics-based assessment for patient-specific risk assessment is a promising approach for clinical management of the disease. Among various factors that affect such assessment, AAA wall thickness is expected to be an important factor. However, regionally varying patient-specific wall thickness has not been incorporated as a modeling feature in AAA biomechanics. To the best our knowledge, the present work is the first to incorporate patient-specific variable wall thickness without an underlying empirical assumption on its distribution for AAA wall mechanics estimation. In this work, we present a novel method for incorporating regionally varying wall thickness (the "PSNUT" modeling strategy) in AAA finite element modeling and the application of this method to a diameter-matched cohort of 28 AAA geometries to assess differences in wall mechanics originating from the conventional assumption of a uniform wall thickness. For the latter, we used both a literature-derived population average wall thickness (1.5 mm; the "UT" strategy) as well as the spatial average of our patient-specific variable wall thickness (the "PSUT" strategy). For the three different wall thickness modeling strategies, wall mechanics were assessed by four biomechanical parameters: the spatial maxima of the first principal stress, strain, strain-energy density, and displacement. A statistical analysis was performed to address the hypothesis that the use of any uniform wall thickness model resulted in significantly different biomechanical parameters compared to a patient-specific regionally varying wall thickness model. Statistically significant differences were obtained with the UT modeling strategy compared to the PSNUT strategy for the spatial maxima of the first principal stress (p ¼ 0.002), strain (p ¼ 0.0005), and strain-energy density (p ¼ 7.83 e-5) but not for displacement (p ¼ 0.773). Likewise, significant differences were obtained comparing the PSUT modeling strategy with the PSNUT strategy for the spatial maxima of the first principal stress (p ¼ 9.68 e-7), strain (p ¼ 1.03 e-8), strain-energy density (p ¼ 9.94 e-8), and displacement (p ¼ 0.0059). No significant differences were obtained comparing the UT and PSUT strategies for the spatial maxima of the first principal stress (p ¼ 0.285), strain (p ¼ 0.152), strain-energy density (p ¼ 0.222), and displacement (p ¼ 0.0981). This work strongly recommends the use of patient-specific regionally varying wall thickness derived from the segmentation of abdominal computed tomography (CT) scans if the AAA finite element analysis is focused on estimating peak biomechanical parameters, such as stress, strain, and strain-energy density.