Real-world influenza vaccine effectiveness:New designs and methods to adjust for confounding and bias

Zoals aanbevolen door de Wereldgezondheidsorganisatie (WHO), is jaarlijkse influenzavaccinatie van groepen met een verhoogd risico op complicaties ten gevolge van een influenza-infectie zoals ouderen en personen met bepaalde medische risicofactoren een van de belangrijkste preventieve maatregelen. In de praktijk is de influenzavaccinatiegraad echter doorgaans laag. Onzekerheid over de werkelijke effectiviteit van het influenzavaccin kan hiervoor de oorzaak zijn. Zowel beperkingen bij het opzetten van gerandomiseerd (placebo)gecontroleerd onderzoek als de gevoeligheid van observationeel onderzoek voor vertekening door verschillende vormen van bias of confounding, kunnen bijdragen aan deze onzekerheid. In dit proefschrift zijn nieuwe onderzoeksopzetten en methoden gebruikt om een meer valide schatting te maken van de influenzavaccinatie effectiviteit (IVE). Hierbij is rekening gehouden met potentiële bias en confounding en zijn de IVE schattingen hiervoor gecorrigeerd. Na correctie voor verschillende soorten bias en potentiële confounders, vonden wij dat influenzavaccinatie redelijk effectief was tegen influenza en complicaties gerelateerd aan influenza. Daarnaast signaleerden wij dat conventionele methoden voor meta-analyses mogelijk niet het beste instrument zijn om de gepoolde IVE te meten en dat het gebruik van betrouwbaardere methoden overwogen moeten worden bij toekomstige studies. Tot slot namen wij, afhankelijk van influenza virus (sub)typen, influenza seizoen en het type controlegroep dat geïncludeerd was in het test-negative design case-control onderzoek, extreme variabiliteit waar tussen de IVE schattingen

Design and Analysis of Extremely Low-Noise MEMS Gyroscopes for Navigation

Inertial measurement sensors that include three gyroscopes and three accelerometers are key elements of inertial navigation systems. Miniaturization of these sensors is desirable to achieve low manufacturing cost, high durability, low weight, small size, and low energy consumption. However, there is a tradeoff between miniaturization of inertial sensors and their performance. Developing all the necessary components for navigation using inertial sensors in a small volume requires major redesign and innovation in these sensors. The main goal of this research is to identify, analyze and optimize parameters that limit the performance of miniaturized inertial gyroscopes and provide comprehensive design guidelines for achieving multi-axis navigation-grade MEMS gyroscopes. It is shown that the fundamental performance limit of inertial gyroscopes is angle random walk (ARW) due to thermo-mechanical and electronic noises. Theoretical models show that resonant frequency, frequency mismatch between sensing and driving modes, effective mass, quality factor (Q), driving amplitude, sensing gap, sensing area and angular gain are the most important parameters that need to be optimized for best noise and most practical device design. In this research, two different structures are considered for low-noise MEMS gyroscopes: 1) shell gyroscopes in yaw direction, and 2) a novel super sensitive stacked (S3) gyroscope for pitch/roll directions. Extensive analytical and FEM numerical modeling was conducted throughout this research to investigate the mechanisms that affect Q and noise in shell resonators used in yaw-rate gyroscopes. These models provided insight into ways to significantly improve resonator design, structure, fabrication, and assembly and helped fabricate fused silica shells with Qs as high as 10 million (at least an order of magnitude larger than other similar shells). Noise performance of these fused silica shell gyroscopes with 5 mm dimeter improved by about two orders of magnitude (< 5×10-3 °/√hr), representing one of the best noise performances reported for a MEMS gyroscope. To build a high-performance MEMS-based planar vibratory pitch/roll gyroscope, it is critical to have a resonator with high Q in the out-of-plane resonant mode. Existing out-of-plane resonators suffer from low Q due to anchor loss or/and thermoelastic dissipation (TED). Increasing the thickness of the out-of-plane resonator reduces TED, but this increases the anchor loss. To reduce anchor loss significantly, a novel structure called S3 is designed. In this structure, two similar resonators are stacked on top of each other and move in opposite directions, thus providing a balanced stacked resonator with reduced anchor loss. The reduction of anchor loss allows larger thickness of silicon S3 gyroscopes, leading to a very low TED. A large-scale model of a stacked balanced resonator is fabricated and tested. The initial results show more than 50 times improvement in Q (measured in air) when resonators are stacked. It is expected that by testing this device in vacuum, Q would improve by more than three orders of magnitude. The S3 design also has an extremely large effective mass, a very large angular gain, a large driving amplitude, a very small sensing gap, and a large sensing area. It is estimated that a 500 µm thick silicon S3 gyroscope provides ARW of about 1.5×10-5 °/√hr (more than two orders of magnitude better performance than a navigation-grade gyroscope). This extraordinary small value can be improved for 1mm thick fused silica to 7.6×10-7 °/√hr if the technology for etching fused silica could be developed in the future.PHDElectrical and Computer EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147701/1/darvishi_1.pd

IMECE2011-63108 ANALYTICAL SOLUTIONS FOR THE STATIC INSTABILITY OF MICRO/NANO MIRRORS UNDER THE COMBINED EFFECT OF CAPILLARY FORCE AND CASIMIR FORCE

ABSTRACT This paper deals with the problem of static instability of Micro/Nano mirrors under the combined effect of capillary force and Casimir force. At the First the governing equations of the statical behavior of Micro/Nano mirrors under the combined effect of capillary force and casimir force is obtained. The dependency of the critical tilting angle on the physical and geometrical parameters of the nano/micromirror and its supporting torsional beams is investigated. It is found that existence of casimir force can considerably reduce the stability limits of nano/micromirror. It is also found that rotation angle of the mirror due to capillary force highly depends on the casimir force applied to the mirror. Finally analytical tool Homotopy Perturbation Method (HPM) is utilized for prediction of the mirror&apos;s behaviour under combined capillary and casimir forces. It is observed that a sixth order perturbation approximation accurately predicts the rotation angle and stability limits of the mirror. Results of this paper can be used for successful fabrication of nano/micromirrors using wet etching process where capillary force plays a major role in the system.

IMECE2011-63112 CLOSED FORM SOLUTIONS FOR THE PROBLEM OF STATICAL BEHAVIOR OF NANO/MICROMIRRORS UNDER THE EFFECT OF CAPILLARY FORCE AND VAN DER WAALS FORCE

ABSTRACT The current paper deals with the problem of static instability of Micro/Nano mirrors under the combined effect of capillary force and van der Waals force. First the governing equations of the statical behavior of Micro/Nano mirrors under the combined effect of capillary force and casimir force is obtained using the newtons first law of motion. The dependence of the critical tilting angle on the physical and geometrical parameters of the nano/micromirror and its supporting torsional beams is investigated. It is found that existence of vdW torque can considerably reduce the stability limits of the nano/micromirror. It is also found that rotation angle of the mirror due to capillary force highly depends on the vdW toque applied to the mirror. Finally analytical tool Homotopy Perturbation Mehtod (HPM) is utilized for prediction of the nano/micromirror behaviour under combined capillary and vdW force. It is observed that a sixth order perturbation approximation accurately predicts the rotation angle and stability limits of the mirror. Results of this paper can be used for successful fabrication of nano/micromirrors using wet etching process where capillary force plays a major role in the system

A case of minimal uterine serous carcinoma with distant lymph node metastasis without peritoneal dissemination

A 61-year old woman underwent total abdominal hysterectomy and pelvic lymph node dissection under the diagnosis of endometrial cancer. Although pelvic lymph nodes were positive for adenocarcinoma with psamomma bodies, no other lesion that was a primary lesion was verified. A postoperative study revealed the existence of para-aortic lymph node and supraclavicular lymph node metastases. Therefore, the endometrial biopsy specimen was reviewed. With the findings of p53 positivity by immunohistochemistry in the papillary part, the final histopathological diagnosis was changed to endometrial serous adenocarcinoma. Postoperative chemotherapy followed by radiotherapy for supraclavicular lymph node metastasis achieved complete response. This type of tumor must be considered in a differential diagnosis when metastatic papillary serous carcinoma is detected, but the primary site remains unknown

INVESTIGATION OF THERMOELASTIC LOSS MECHANISM IN SHELL RESONATORS

ABSTRACT Maximizing quality (Q) factor is key to enhancing the performance of micro mechanical resonators, which are used in a wide range of applications such as gyroscopes, filters, and clocks. There are several energy loss mechanisms commonly associated with micro resonators including anchor loss through the substrate, squeeze film damping, thermoelastic dissipation (TED), and surface loss. This work focuses on the thermoelastic loss as one of the major energy dissipation mechanisms of micro shell resonators. In this article, the effects of material properties, thickness, conductive coating and operating temperature on the Q-factor of micro shell resonators are investigated. Numerical simulation shows shell resonators have higher Q-factors when they are operating at lower temperatures. Although, the magnitude of the simulated Q-factors of an uncoated bare resonator made from fused silica is more than 70 million and so it is too high to have a remarkable effect on the total Q-factor, our study shows that even a thin layer of some conductive coatings like gold on the surface of a bare shell reduces Q-factor significantly. The sensitivity of the coated shell resonator design to the TED phenomenon provides useful information for the development of new micro shell resonators with improved performance and Q-factors

Influenza vaccine effectiveness estimates in the Dutch population from 2003 to 2014:The test-negative design case-control study with different control groups

Information about influenza vaccine effectiveness (IVE) is important for vaccine strain selection and immunization policy decisions. The test-negative design (TND) case-control study is commonly used to obtain IVE estimates. However, the definition of the control patients may influence IVE estimates. We have conducted a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database which includes data from patients who consulted the General Practitioner (GP) for an episode of acute influenza-like illness (ILI) or acute respiratory infection (ARI) with known influenza vaccination status. Cases were patients tested positive for influenza virus. Controls were grouped into those who tested (1) negative for influenza virus (all influenza negative), (2) negative for influenza virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus (non-influenza virus positive), and (3) negative for these four viruses (pan-negative). We estimated the IVE over all epidemic seasons from 2003/2004 through 2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched seasons and the individual seasons using generalized linear mixed-effect and multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15-48), 64% (95% CI: 49-75) and 21% (95% CI: -1 to 39) for all influenza negative, non-influenza virus positive and pan-negative controls, respectively. In both the main and subgroup analyses IVE estimates were the highest using non-influenza virus positive controls, likely due to limiting inclusion of controls without laboratory-confirmation of a virus causing the respiratory disease

Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients

<p>Abstract</p> <p>Background</p> <p>Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression.</p> <p>Methods</p> <p>The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients.</p> <p>Results</p> <p>Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients.</p> <p>Conclusion</p> <p>Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.</p