Reporting on methods of subgroup analysis in clinical trials: a survey of four scientific journals

Results of subgroup analysis (SA) reported in randomized clinical trials (RCT) cannot be adequately interpreted without information about the methods used in the study design and the data analysis. Our aim was to show how often inaccurate or incomplete reports occur. First, we selected eight methodological aspects of SA on the basis of their importance to a reader in determining the confidence that should be placed in the author's conclusions regarding such analysis. Then, we reviewed the current practice of reporting these methodological aspects of SA in clinical trials in four leading journals, i.e., the New England Journal of Medicine, the Journal of the American Medical Association, the Lancet, and the American Journal of Public Health. Eight consecutive reports from each journal published after July 1, 1998 were included. Of the 32 trials surveyed, 17 (53%) had at least one SA. Overall, the proportion of RCT reporting a particular methodological aspect ranged from 23 to 94%. Information on whether the SA preceded/followed the analysis was reported in only 7 (41%) of the studies. Of the total possible number of items to be reported, NEJM, JAMA, Lancet and AJPH clearly mentioned 59, 67, 58 and 72%, respectively. We conclude that current reporting of SA in RCT is incomplete and inaccurate. The results of such SA may have harmful effects on treatment recommendations if accepted without judicious scrutiny. We recommend that editors improve the reporting of SA in RCT by giving authors a list of the important items to be reported.

Comparison of methods for urinary albumin determination in patients with type 1 diabetes

We tested the correlation of the albumin-to-creatinine ratio (A/C) in an early-morning urine sample, measured with a commercial kit (DCA 2000®), with the conventional immunoturbidimetric determination in the laboratory and with overnight albumin excretion rate (reference method). Fifty-five type 1 diabetic adolescents had their first-morning urine collected on the 1st and 8th day of the period. Urinary albumin and creatinine were determined immediately using the DCA 2000® kit. Samples were also stored for laboratory analysis. To evaluate the correlation between early-morning urinary A/C ratio and overnight albumin excretion rate, 16 subjects had a timed overnight urine collection. A/C ratios determined with the DCA 2000® kit and by the laboratory method were 13.1 ± 20.5 and 20.4 ± 46.3 mg/g, respectively. A/C results by both methods proved to be strongly correlated (r = 0.98, P<0.001). DCA 2000®-determined A/C showed 50% sensitivity and 100% specificity when compared to the reference method. Spot urinary A/C of the subset of 16 subjects significantly correlated with their overnight albumin excretion rate (r = 0.98, P<0.001). Intraindividual variation ranged from 17 to 32% and from 9 to 63% for A/C and overnight albumin excretion rate, respectively. In conclusion, an early-morning specimen should be used instead of timed overnight urine and the A/C ratio is an accurate, reliable and easily determined parameter for the screening of diabetic nephropathy. Immediate measurement of the A/C ratio is feasible using the DCA 2000® kit. Intraindividual variability indicates the need for repeated determinations to confirm microalbuminuria and the diagnosis of incipient diabetic nephropathy.

Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks

Our aim was to compare the clinical features of panic disorder (PD) patients sensitive to hyperventilation or breath-holding methods of inducing panic attacks. Eighty-five PD patients were submitted to both a hyperventilation challenge test and a breath-holding test. They were asked to hyperventilate (30 breaths/min) for 4 min and a week later to hold their breath for as long as possible, four times with a 2-min interval. Anxiety scales were applied before and after the tests. We selected the patients who responded with a panic attack to just one of the tests, i.e., those who had a panic attack after hyperventilating (HPA, N = 24, 16 females, 8 males, mean age ± SD = 38.5 ± 12.7 years) and those who had a panic attack after breath holding (BHPA, N = 20, 11 females, 9 males, mean age ± SD = 42.1 ± 10.6 years). Both groups had similar (chi² = 1.28, d.f. = 1, P = 0.672) respiratory symptoms (fear of dying, chest/pain disconfort, shortness of breath, paresthesias, and feelings of choking) during a panic attack. The criteria of Briggs et al. [British Journal of Psychiatry, 1993; 163: 201-209] for respiratory PD subtype were fulfilled by 18 (75.0%) HPA patients and by 14 (70.0%) BHPA patients. The HPA group had a later onset of the disease compared to BHPA patients (37.9 ± 11.0 vs 21.3 ± 12.9 years old, Mann-Whitney, P < 0.001), and had a higher family prevalence of PD (70.8 vs 25.0%, chi² = 19.65, d.f. = 1, P = 0.041). Our data suggest that these two groups - HPA and BHPA patients - may be specific subtypes of PD.

Statistical segmentation methods and color variance analysis of retinal images

In this research, the effectiveness of Naive Bayes and Gaussian Mixture Models classifiers on segmenting exudates in retinal images is studied and the results are evaluated with metrics commonly used in medical imaging. Also, a color variation analysis of retinal images is carried out to find how effectively can retinal images be segmented using only the color information of the pixels.

Novel virtual environment and real-time simulation based methods for improving life-cycle efficiency of non-road mobile machinery

Virtual environments and real-time simulators (VERS) are becoming more and more important tools in research and development (R&D) process of non-road mobile machinery (NRMM). The virtual prototyping techniques enable faster and more cost-efficient development of machines compared to use of real life prototypes. High energy efficiency has become an important topic in the world of NRMM because of environmental and economic demands. The objective of this thesis is to develop VERS based methods for research and development of NRMM. A process using VERS for assessing effects of human operators on the life-cycle efficiency of NRMM was developed. Human in the loop simulations are ran using an underground mining loader to study the developed process. The simulations were ran in the virtual environment of the Laboratory of Intelligent Machines of Lappeenranta University of Technology. A physically adequate real-time simulation model of NRMM was shown to be reliable and cost effective in testing of hardware components by the means of hardware-in-the-loop (HIL) simulations. A control interface connecting integrated electro-hydraulic energy converter (IEHEC) with virtual simulation model of log crane was developed. IEHEC consists of a hydraulic pump-motor and an integrated electrical permanent magnet synchronous motorgenerator. The results show that state of the art real-time NRMM simulators are capable to solve factors related to energy consumption and productivity of the NRMM. A significant variation between the test drivers is found. The results show that VERS can be used for assessing human effects on the life-cycle efficiency of NRMM. HIL simulation responses compared to that achieved with conventional simulation method demonstrate the advances and drawbacks of various possible interfaces between the simulator and hardware part of the system under study. Novel ideas for arranging the interface are successfully tested and compared with the more traditional one. The proposed process for assessing the effects of operators on the life-cycle efficiency will be applied for wider group of operators in the future. Driving styles of the operators can be analysed statistically from sufficient large result data. The statistical analysis can find the most life-cycle efficient driving style for the specific environment and machinery. The proposed control interface for HIL simulation need to be further studied. The robustness and the adaptation of the interface in different situations must be verified. The future work will also include studying the suitability of the IEHEC for different working machines using the proposed HIL simulation method.

Balancing the quotation process by LEAN methods

This thesis studies the possibility to use lean tools and methods in a quotation process which is carried out in an office environment. The aim of the study was to find out and test the relevant lean tools and methods which can help to balance and standardize the quotation process, and reduce the variance in quotation lead times and in quality. Seminal works, researches and guide books related to the topic were used as the basis for the theory development. Based on the literature review and the case company’s own lean experience, the applicable lean tools and methods were selected to be tested by a sales support team. Leveling production, by product categorization and value stream mapping, was a key method to be used to balance the quotation process. 5S method was started concurrently for standardizing the work. Results of the testing period showed that lean tools and methods are applicable in office process and selected tools and methods helped to balance and standardize the quotation process. Case company’s sales support team decided to implement new lean based quotation process model.

Lean Methods and Digital Technologies in Healtchare

The experiences of several healthcare organizations were considered to distinguish the most frequently used lean tools, the success and failure factors, and the obstacles that may appear while implementing lean. As a result, two approaches to “go lean” were defined, and analyzed from the prospective of the applicability to healthcare processes. Industrialization of healthcare was studied, and the most promising digital technology tools to improve healthcare process were highlighted. Finally, the analysis of healthcare challenges and feasible ways to address them was conducted and presented as the main result of this work. The possible ways of implementation of the findings and limitations were described in the conclusion.

Power efficiency estimation and simulation of different control methods for the rotary screw compressor

Nowadays the energy efficiency has become one of the most concerned topics. Compressors are the equipment, which is very common in industry. Moreover, they tend to operate during long cycles and therefore even small decrease in power consumption can significantly reduce electricity costs during the year. And therefore it is important to investigate ways of increasing the energy efficiency of the compressors. In the thesis rotary screw compressor alongside with different control approaches is described. Simulation models for various control types of rotary screw compressor are developed. Analysis of laboratory equipment is conducted and results are compared with simulation. Suggestions of the real laboratory equipment improvement are given.

Behavioral and physiological methods for early quantitative assessment of spinal cord injury and prognosis in rats

Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.

Comparison of anaerobic threshold determined by visual and mathematical methods in healthy women

Several methods are used to estimate anaerobic threshold (AT) during exercise. The aim of the present study was to compare AT obtained by a graphic visual method for the estimate of ventilatory and metabolic variables (gold standard), to a bi-segmental linear regression mathematical model of Hinkley's algorithm applied to heart rate (HR) and carbon dioxide output (VCO2) data. Thirteen young (24 ± 2.63 years old) and 16 postmenopausal (57 ± 4.79 years old) healthy and sedentary women were submitted to a continuous ergospirometric incremental test on an electromagnetic braking cycloergometer with 10 to 20 W/min increases until physical exhaustion. The ventilatory variables were recorded breath-to-breath and HR was obtained beat-to-beat over real time. Data were analyzed by the nonparametric Friedman test and Spearman correlation test with the level of significance set at 5%. Power output (W), HR (bpm), oxygen uptake (VO2; mL kg-1 min-1), VO2 (mL/min), VCO2 (mL/min), and minute ventilation (VE; L/min) data observed at the AT level were similar for both methods and groups studied (P > 0.05). The VO2 (mL kg-1 min-1) data showed significant correlation (P < 0.05) between the gold standard method and the mathematical model when applied to HR (r s = 0.75) and VCO2 (r s = 0.78) data for the subjects as a whole (N = 29). The proposed mathematical method for the detection of changes in response patterns of VCO2 and HR was adequate and promising for AT detection in young and middle-aged women, representing a semi-automatic, non-invasive and objective AT measurement.

New methods for controlling twin configurations and characterizing twin boundaries in 5M Ni-Mn-Ga for the development of applications

Traditional methods for studying the magnetic shape memory (MSM) alloys Ni-Mn-Ga include subjecting the entire sample to a uniform magnetic field or completely actuating the sample mechanically. These methods have produced significant results in characterizing the MSM effect, the properties of Ni-Mn-Ga and have pioneered the development of applications from this material. Twin boundaries and their configuration within a Ni-Mn-Ga sample are a key component in the magnetic shape memory effect. Applications that are developed require an understanding of twin boundary characteristics and, more importantly, the ability to predictably control them. Twins have such a critical role that the twinning stress of a Ni-Mn-Ga crystal is the defining characteristic that indicates its quality and significant research has been conducted to minimize this property. This dissertation reports a decrease in the twinning stress, predictably controlling the twin configuration and characterizing the dynamics of twin boundaries. A reduction of the twinning stress is demonstrated by the discovery of Type II twins within Ni-Mn-Ga which have as little as 10% of the twinning stress of traditional Type I twins. Furthermore, new methods of actuating a Ni-Mn-Ga element using localized unidirectional or bidirectional magnetic fields were developed that can predictably control the twin configuration in a localized area of a Ni-Mn-Ga element. This method of controlling the local twin configuration was used in the characterization of twin boundary dynamics. Using a localized magnetic pulse, the velocity and acceleration of a single twin boundary were measured to be 82.5 m/s and 2.9 × 107 m/s2, and the time needed for the twin boundary to nucleate and begin moving was less than 2.8 μs. Using a bidirectional magnetic field from a diametrically magnetized cylindrical magnet, a highly reproducible and controllable local twin configuration was created in a Ni-Mn-Ga element which is the fundamental pumping mechanism in the MSM micropump that has been co-invented and extensively characterized by the author.

Novel control, haptic and calibration methods for teleoperated electrohydraulic servo systems

The aim of this thesis is to propose a novel control method for teleoperated electrohydraulic servo systems that implements a reliable haptic sense between the human and manipulator interaction, and an ideal position control between the manipulator and the task environment interaction. The proposed method has the characteristics of a universal technique independent of the actual control algorithm and it can be applied with other suitable control methods as a real-time control strategy. The motivation to develop this control method is the necessity for a reliable real-time controller for teleoperated electrohydraulic servo systems that provides highly accurate position control based on joystick inputs with haptic capabilities. The contribution of the research is that the proposed control method combines a directed random search method and a real-time simulation to develop an intelligent controller in which each generation of parameters is tested on-line by the real-time simulator before being applied to the real process. The controller was evaluated on a hydraulic position servo system. The simulator of the hydraulic system was built based on Markov chain Monte Carlo (MCMC) method. A Particle Swarm Optimization algorithm combined with the foraging behavior of E. coli bacteria was utilized as the directed random search engine. The control strategy allows the operator to be plugged into the work environment dynamically and kinetically. This helps to ensure the system has haptic sense with high stability, without abstracting away the dynamics of the hydraulic system. The new control algorithm provides asymptotically exact tracking of both, the position and the contact force. In addition, this research proposes a novel method for re-calibration of multi-axis force/torque sensors. The method makes several improvements to traditional methods. It can be used without dismantling the sensor from its application and it requires smaller number of standard loads for calibration. It is also more cost efficient and faster in comparison to traditional calibration methods. The proposed method was developed in response to re-calibration issues with the force sensors utilized in teleoperated systems. The new approach aimed to avoid dismantling of the sensors from their applications for applying calibration. A major complication with many manipulators is the difficulty accessing them when they operate inside a non-accessible environment; especially if those environments are harsh; such as in radioactive areas. The proposed technique is based on design of experiment methodology. It has been successfully applied to different force/torque sensors and this research presents experimental validation of use of the calibration method with one of the force sensors which method has been applied to.

Comparison of Model-Based Flow Rate Estimation Methods in Frequency-Converter-Driven Pumps and Fans

Fluid handling systems such as pump and fan systems are found to have a significant potential for energy efficiency improvements. To deliver the energy saving potential, there is a need for easily implementable methods to monitor the system output. This is because information is needed to identify inefficient operation of the fluid handling system and to control the output of the pumping system according to process needs. Model-based pump or fan monitoring methods implemented in variable speed drives have proven to be able to give information on the system output without additional metering; however, the current model-based methods may not be usable or sufficiently accurate in the whole operation range of the fluid handling device. To apply model-based system monitoring in a wider selection of systems and to improve the accuracy of the monitoring, this paper proposes a new method for pump and fan output monitoring with variable-speed drives. The method uses a combination of already known operating point estimation methods. Laboratory measurements are used to verify the benefits and applicability of the improved estimation method, and the new method is compared with five previously introduced model-based estimation methods. According to the laboratory measurements, the new estimation method is the most accurate and reliable of the model-based estimation methods.

Comparison of methods by TLC and HPTLC for determination of aflatoxin M1 in milk and B1 in eggs

Milk and egg matrixes were assayed for aflatoxin M1 (AFM1) and B1 (AFB1) respectively, by AOAC official and modified methods with detection and quantification by thin layer chromatography (TLC) and high performance thin layer chromatography (HPTLC). The modified methods: Blanc followed by Romer, showed to be most appropriate for AFM1 analysis in milk. Both methods reduced emulsion formation, produced cleaner extracts, no streaking spots, precision and accuracy improved, especially when quantification was performed by HPTLC. The use of ternary mixture in the Blanc Method was advantageous as the solvent could extract AFM1 directly from the first stage (extraction), leaving other compounds in the binary mixture layer, avoiding emulsion formation, thus reducing toxin loss. The relative standard deviation (RSD%) values were low, 16 and 7% when TLC and HPTLC were used, with a mean recovery of 94 and 97%, respectively. As far as egg matrix and final extract are concerned, both methods evaluated for AFB1 need further studies. Although that matrix leads to emulsion with consequent loss of toxin, the Romer modified presented a reasonable clean extract (mean recovery of 92 and 96% for TLC and HPTLC, respectively). Most of the methods studied did not performed as expected mainly due to the matrixes high content of triglicerides (rich on saturated fatty acids), cholesterol, carotene and proteins. Although nowadays most methodology for AFM1 is based on HPLC, TLC determination (Blanc and Romer modified) for AFM1 and AFB1 is particularly recommended to those, inexperienced in food and feed mycotoxins analysis and especially who cannot afford to purchase sophisticated (HPLC,HPTLC) instrumentation.

Thick Section Laser Beam Welding of Structural Steels: Methods for Improving Welding Efficiency

Laser beam welding (LBW) is applicable for a wide range of industrial sectors and has a history of fifty years. However, it is considered an unusual method with applications typically limited to welding of thin sheet metal. With a new generation of high power lasers there has been a renewed interest in thick section LBW (also known as keyhole laser welding). There was a growing body of publications during 2001-2011 that indicates an increasing interest in laser welding for many industrial applications, and in last ten years, an increasing number of studies have examined the ways to increase the efficiency of the process. Expanding the thickness range and efficiency of LBW makes the process a possibility for industrial applications dealing with thick metal welding: shipbuilding, offshore structures, pipelines, power plants and other industries. The advantages provided by LBW, such as high process speed, high productivity, and low heat input, may revolutionize these industries and significantly reduce the process costs. The research to date has focused on either increasing the efficiency via optimizing process parameters, or on the process fundamentals, rather than on process and workpiece modifications. The argument of this thesis is that the efficiency of the laser beam process can be increased in a straightforward way in the workshop conditions. Throughout this dissertation, the term “efficiency” is used to refer to welding process efficiency, specifically, an increase in efficiency refers an increase in weld’s penetration depth without increasing laser power level or decreasing welding speed. These methods are: modifications of the workpiece – edge surface roughness and air gap between the joining plates; modification of the ambient conditions – local reduction of the pressure in the welding zone; modification of the welding process – preheating of the welding zone. Approaches to improve the efficiency are analyzed and compared both separately and combined. These experimentally proven methods confirm previous findings and contribute additional evidence which expand the opportunities for laser beam welding applications. The focus of this research was primarily on the effects of edge surface roughness preparation and pre-set air gap between the plates on weld quality and penetration depth. To date, there has been no reliable evidence that such modifications of the workpiece give a positive effect on the welding efficiency. Other methods were tested in combination with the two methods mentioned above. The most promising - combining with reduced pressure method - resulted in at least 100% increase in efficiency. The results of this thesis support the idea that joining those methods in one modified process will provide the modern engineering with a sufficient tool for many novel applications with potential benefits to a range of industries.