Fixed-Width Output Analysis for Markov Chain Monte Carlo

Markov chain Monte Carlo is a method of producing a correlated sample in order to estimate features of a complicated target distribution via simple ergodic averages. A fundamental question in MCMC applications is when should the sampling stop? That is, when are the ergodic averages good estimates of the desired quantities? We consider a method that stops the MCMC sampling the first time the width of a confidence interval based on the ergodic averages is less than a user-specified value. Hence calculating Monte Carlo standard errors is a critical step in assessing the output of the simulation. In particular, we consider the regenerative simulation and batch means methods of estimating the variance of the asymptotic normal distribution. We describe sufficient conditions for the strong consistency and asymptotic normality of both methods and investigate their finite sample properties in a variety of examples.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

[Titanium-alloy vs. CoCr-alloy in removable prosthodontics--a clinical study]

Different types of titanium-alloys instead of CoCr-alloys have been tested as material for the framework of removable partial dentures (RPD). Adequate casting and processing techniques have been developed which enable to fabricate frameworks of complex designs and the problem limits porosity. This opened new possibilities for the use of titanium-alloys with improved properties (E-module). The aim of this study was to summarise the use of titanium in removable prosthodontics and to evaluate prospectively the use of the Ti6A17Nb-alloy for RPDs in a small group of patients. Two identically designed RPDs from CoCr-alloy (remanium GM 800+) and Ti6A17Nb-alloy (girotan L) were produced for ten patients. They had to wear each RPD during six months, first the CoCr-RPD and then the Ti6A17Nb-RPD. A questionnaire (visual analogue scale = VAS) was completed by the patients after one, three and six months of function for each RPD. Prosthetic complications and service needed were recorded. After the end of the entire observation period of twelve months, the patients remained with the Ti6A17Nb-RPD and answered the questionnaire after another six months. All parameters regarding the design of the RPDs were positively estimated by the dentist. Minimal, not significant differences were noted by the patients concerning comfort, stability and retention (VAS). Clinically, no differences in technical aspects or regarding biological complications were observed after six-months periods. The Ti6A17Nb-alloy (girotan L) for the framework of RPDs was judged by patients and professionals to be equivalent to RPDs made from CoCr-alloy. No differences in material aspects could objectively be observed. The Ti6A17Nb-alloy can be beneficial for patients with allergies or incompatibility with one or several components of the CoCr-alloy.

[Zirconia and removable partial dentures]

The present paper deals with the double crown technique in removable prosthodontics. New ceramic materials like zirconia are increasingly used in combination with CAD/CAM technologies for framework fabrication of fixed prosthesis, tooth- or implant-supported. However, zirconia is also a newly accepted material in removable prosthodontics. It replaces gold alloys for the fabrication of primary telescopic crowns. The Galvanoforming technology is preferably used to fabricate the secondary crowns. The combination of both techniques and materials results in a prosthetic reconstruction of high quality, optimum fit and good biocompatibility.

Prosthetic considerations

Implants have changed prosthodontics more than any other innovation in dentistry. Replacement of lost teeth by a fixed or removable prosthesis is considered to be a restitutio ad similem, while implants may provide a feeling of restitutio ad integrum. Implant prosthodontics means restoring function, aesthetics, and providing technology; biology and technology are combined. Placement of implants is a reconstructive, preprosthetic surgical intervention and is therefore different from most goals in oral surgery that consist of tooth extraction, treating infection and removing pathology from soft or hard tissues. Thus, implants are part of the final prosthetic treatment which encompasses functional, aesthetic and social rehabilitation. The patient's needs and functional status determine the goal of prosthetic treatment. Treatment outcomes in implant prosthodontics are survival of implants and prostheses, impact on physiological and psychological status, oral health-related impact on quality of life, and initial and maintenance costs. A variety of prosthetic solutions are available to restore the partially and completely edentulous jaw and more recently specific methods have been developed such as computer guided planning and CAD-CAM technologies. These should allow more uniform quality and passive fit of prostheses, and simultaneously enables processing of biologically well-accepted materials.

Expression profiling with RNA from formalin-fixed, paraffin-embeeded material

Background Molecular characterization of breast and other cancers by gene expression profiling has corroborated existing classifications and revealed novel subtypes. Most profiling studies are based on fresh frozen (FF) tumor material which is available only for a limited number of samples while thousands of tumor samples exist as formalin-fixed, paraffin-embedded (FFPE) blocks. Unfortunately, RNA derived of FFPE material is fragmented and chemically modified impairing expression measurements by standard procedures. Robust protocols for isolation of RNA from FFPE material suitable for stable and reproducible measurement of gene expression (e.g. by quantitative reverse transcriptase PCR, QPCR) remain a major challenge. Results We present a simple procedure for RNA isolation from FFPE material of diagnostic samples. The RNA is suitable for expression measurement by QPCR when used in combination with an optimized cDNA synthesis protocol and TaqMan assays specific for short amplicons. The FFPE derived RNA was compared to intact RNA isolated from the same tumors. Preliminary scores were computed from genes related to the ER response, HER2 signaling and proliferation. Correlation coefficients between intact and partially fragmented RNA from FFPE material were 0.83 to 0.97. Conclusion We developed a simple and robust method for isolating RNA from FFPE material. The RNA can be used for gene expression profiling. Expression measurements from several genes can be combined to robust scores representing the hormonal or the proliferation status of the tumor.

Fixed block configuration GDDs with block size 6 and (3, r)-regular graphs

Chapter 1 is used to introduce the basic tools and mechanics used within this thesis. Most of the definitions used in the thesis will be defined, and we provide a basic survey of topics in graph theory and design theory pertinent to the topics studied in this thesis. In Chapter 2, we are concerned with the study of fixed block configuration group divisible designs, GDD(n; m; k; λ1; λ2). We study those GDDs in which each block has configuration (s; t), that is, GDDs in which each block has exactly s points from one of the two groups and t points from the other. Chapter 2 begins with an overview of previous results and constructions for small group size and block sizes 3, 4 and 5. Chapter 2 is largely devoted to presenting constructions and results about GDDs with two groups and block size 6. We show the necessary conditions are sufficient for the existence of GDD(n, 2, 6; λ1, λ2) with fixed block configuration (3; 3). For configuration (1; 5), we give minimal or nearminimal index constructions for all group sizes n ≥ 5 except n = 10, 15, 160, or 190. For configuration (2, 4), we provide constructions for several families ofGDD(n, 2, 6; λ1, λ2)s. Chapter 3 addresses characterizing (3, r)-regular graphs. We begin with providing previous results on the well studied class of (2, r)-regular graphs and some results on the structure of large (t; r)-regular graphs. In Chapter 3, we completely characterize all (3, 1)-regular and (3, 2)-regular graphs, as well has sharpen existing bounds on the order of large (3, r)- regular graphs of a certain form for r ≥ 3. Finally, the appendix gives computational data resulting from Sage and C programs used to generate (3, 3)-regular graphs on less than 10 vertices.

Effects of fixed night shift work on 24 hour blood pressure regulation, state anxiety levels and total sleep time

Nearly 22 million Americans operate as shift workers, and shift work has been linked to the development of cardiovascular disease (CVD). This study is aimed at identifying pivotal risk factors of CVD by assessing 24 hour ambulatory blood pressure, state anxiety levels and sleep patterns in 12 hour fixed shift workers. We hypothesized that night shift work would negatively affect blood pressure regulation, anxiety levels and sleep patterns. A total of 28 subjects (ages 22-60) were divided into two groups: 12 hour fixed night shift workers (n=15) and 12 hour fixed day shift workers (n=13). 24 hour ambulatory blood pressure measurements (Space Labs 90207) were taken twice: once during a regular work day and once on a non-work day. State anxiety levels were assessed on both test days using the Speilberger’s State Trait Anxiety Inventory. Total sleep time (TST) was determined using self recorded sleep diary. Night shift workers demonstrated increases in 24 hour systolic (122 ± 2 to 126 ± 2 mmHg, P=0.012); diastolic (75 ± 1 to 79 ± 2 mmHg, P=0.001); and mean arterial pressures (90 ± 2 to 94 ± 2mmHg, P<0.001) during work days compared to off days. In contrast, 24 hour blood pressures were similar during work and off days in day shift workers. Night shift workers reported less TST on work days versus off days (345 ± 16 vs. 552 ± 30 min; P<0.001), whereas day shift workers reported similar TST during work and off days (475 ± 16 minutes to 437 ± 20 minutes; P=0.231). State anxiety scores did not differ between the groups or testing days (time*group interaction P=0.248), suggesting increased 24 hour blood pressure during night shift work is related to decreased TST, not short term anxiety. Our findings suggest that fixed night shift work causes disruption of the normal sleep-wake cycle negatively affecting acute blood pressure regulation, which may increase the long-term risk for CVD.

AN EXPERIMENTAL STUDY OF PARTIAL LOW RISK DEPLOYMENT IN A FIXED VEHICLE ENVIRONMENT

This study will look at the passenger air bag (PAB) performance in a fix vehicle environment using Partial Low Risk Deployment (PLRD) as a strategy. This development will follow test methods against actual baseline vehicle data and Federal Motor Vehicle Safety Standards 208 (FMVSS 208). FMVSS 208 states that PAB compliance in vehicle crash testing can be met using one of three deployment methods. The primary method suppresses PAB deployment, with the use of a seat weight sensor or occupant classification sensor (OCS), for three-year old and six-year old occupants including the presence of a child seat. A second method, PLRD allows deployment on all size occupants suppressing only for the presents of a child seat. A third method is Low Risk Deployment (LRD) which allows PAB deployment in all conditions, all statures including any/all child seats. This study outlines a PLRD development solution for achieving FMVSS 208 performance. The results of this study should provide an option for system implementation including opportunities for system efficiency and other considerations. The objective is to achieve performance levels similar too or incrementally better than the baseline vehicles National Crash Assessment Program (NCAP) Star rating. In addition, to define systemic flexibility where restraint features can be added or removed while improving occupant performance consistency to the baseline. A certified vehicles’ air bag system will typically remain in production until the vehicle platform is redesigned. The strategy to enable the PLRD hypothesis will be to first match the baseline out of position occupant performance (OOP) for the three and six-year old requirements. Second, improve the 35mph belted 5th percentile female NCAP star rating over the baseline vehicle. Third establish an equivalent FMVSS 208 certification for the 25mph unbelted 50th percentile male. FMVSS 208 high-speed requirement defines the federal minimum crash performance required for meeting frontal vehicle crash-test compliance. The intent of NCAP 5-Star rating is to provide the consumer with information about crash protection, beyond what is required by federal law. In this study, two vehicles segments were used for testing to compare and contrast to their baseline vehicles performance. Case Study 1 (CS1) used a cross over vehicle platform and Case Study 2 (CS2) used a small vehicle segment platform as their baselines. In each case study, the restraints systems were from different restraint supplier manufactures and each case contained that suppliers approach to PLRD. CS1 incorporated a downsized twins shaped bag, a carryover inflator, standard vents, and a strategic positioned bag diffuser to help disperse the flow of gas to improve OOP. The twin shaped bag with two segregated sections (lobes) to enabled high-speed baseline performance correlation on the HYGE Sled. CS2 used an A-Symmetric (square shape) PAB with standard size vents, including a passive vent, to obtain OOP similar to the baseline. The A-Symmetric shape bag also helped to enabled high-speed baseline performance improvements in HYGE Sled testing in CS2. The anticipated CS1 baseline vehicle-pulse-index (VPI) target was in the range of 65-67. However, actual dynamic vehicle (barrier) testing was overshadowed with the highest crash pulse from the previous tested vehicles with a VPI of 71. The result from the 35mph NCAP Barrier test was a solid 4-Star (4.7 Star) respectfully. In CS2, the vehicle HYGE Sled development VPI range, from the baseline was 61-62 respectively. Actual NCAP test produced a chest deflection result of 26mm versus the anticipated baseline target of 12mm. The initial assessment of this condition was thought to be due to the vehicles significant VPI increase to 67. A subsequent root cause investigation confirmed a data integrity issue due to the instrumentation. In an effort to establish a true vehicle test data point a second NCAP test was performed but faced similar instrumentation issues. As a result, the chest deflect hit the target of 12.1mm; however a femur load spike, similar to the baseline, now skewed the results. With noted level of performance improvement in chest deflection, the NCAP star was assessed as directional for 5-Star capable performance. With an actual rating of 3-Star due to instrumentation, using data extrapolation raised the ratings to 5-Star. In both cases, no structural changes were made to the surrogate vehicle and the results in each case matched their perspective baseline vehicle platforms. These results proved the PLRD is viable for further development and production implementation.