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

Agreement between self-report and administrative health data on occurrence of non-cancer chronic disease among participants of the BC generations project

Population-based studies of non-cancer chronic disease often rely on self-reported data for disease diagnosis, which may be incomplete, unreliable and suffer from bias. Recently, the British Columbia Generations Project (BCGP; n = 29,736) linked self-reported chronic disease history data to a Chronic Disease Registry (CDR) that applied algorithms to administrative health data to ascertain diagnoses of multiple chronic diseases in the Province of British Columbia. For the 10 diseases captured by both self-report and the CDR, including asthma, chronic obstructive pulmonary disease (COPD), diabetes, hypertension, multiple sclerosis, myocardial infarction, osteoarthritis, osteoporosis, rheumatoid arthritis, and stroke, we calculated Cohen's kappa coefficient to examine concordance of chronic disease status (i.e., ever/never diagnosed) between the data sources. Using CDR data as the gold standard, we also calculated sensitivity, specificity, and positive-predictive value (PPV) for self-reported chronic disease occurrence. The prevalence of each chronic disease was similar across both data sources. Substantial levels of concordance (0.66–0.73) and moderate to high sensitivities (0.64–0.92), specificities (0.98–0.99) and PPVs (0.55–0.84) were observed for diabetes, hypertension, multiple sclerosis, and myocardial infarction. We did observe degree of concordance to vary by age, sex, body mass index (BMI), health perception, and ethnicity across most of the chronic diseases that were evaluated. While administrative health data are imperfect, they are less likely to suffer from bias, making them a reasonable gold standard. Our results demonstrate that for at least some chronic diseases, self-report may be a reasonable method for case ascertainment. However, characteristics of the study population will likely have impacts on the quality of the data

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

TERT, BRAF, and NRAS Mutational Heterogeneity between Paired Primary and Metastatic Melanoma Tumors.

Mutational heterogeneity can contribute to therapeutic resistance in solid cancers. In melanoma, the frequencies of intertumoral and intratumoral heterogeneity are controversial. We examined mutational heterogeneity within individual patients with melanoma using multiplatform analysis of commonly mutated driver and nonpassenger genes. We analyzed paired primary and metastatic tumors from 60 patients and multiple metastatic tumors from 39 patients whose primary tumors were unavailable (n&nbsp;= 271 tumors). We used a combination of multiplex SNaPshot assays, Sanger sequencing, mutation-specific PCR, or droplet digital PCR to determine the presence of BRAFV600, NRASQ61, TERT-124C&gt;T, and TERT-146C&gt;T mutations. Mutations were detected in BRAF (39%), NRAS (21%), and/or TERT (78%). Thirteen patients had TERTmutant discordant tumors; seven of these had a single tumor with both TERT-124C&gt;T and TERT-146C&gt;T mutations present at different allele frequencies. Two patients had both BRAF and NRAS mutations; one had different tumors and the other had a single tumor with both mutations. One patient with a BRAFmutant primary lacked mutant BRAF in at least one of their metastases. Overall, we identified mutational heterogeneity in 18 of 99 patients (18%). These results suggest that some primary melanomas may be composed of subclones with differing mutational profiles. Such heterogeneity may be relevant to treatment responses and survival outcomes