Estimating equations with nonignorably missing response data

Troxel, Lipsitz, and Brennan (1997, Biometrics 53, 857-869) considered parameter estimation from survey data with nonignorable nonresponse and proposed weighted estimating equations to remove the biases in the complete-case analysis that ignores missing observations. This paper suggests two alternative modifications for unbiased estimation of regression parameters when a binary outcome is potentially observed at successive time points. The weighting approach of Robins, Rotnitzky, and Zhao (1995, Journal of the American Statistical Association 90, 106-121) is also modified to obtain unbiased estimating functions. The suggested estimating functions are unbiased only when the missingness probability is correctly specified, and misspecification of the missingness model will result in biases in the estimates. Simulation studies are carried out to assess the performance of different methods when the covariate is binary or normal. For the simulation models used, the relative efficiency of the two new methods to the weighting methods is about 3.0 for the slope parameter and about 2.0 for the intercept parameter when the covariate is continuous and the missingness probability is correctly specified. All methods produce substantial biases in the estimates when the missingness model is misspecified or underspecified. Analysis of data from a medical survey illustrates the use and possible differences of these estimating functions.

Aging-in-place: Perspectives from the construction industry

Older adults report a desire to remain within the preferred environment for as long as possible. This desire is referred to as aging-in-place. Aging-in-place integrates housing and care options. Factors affecting the ability to remain within the preferred environment include current home designs, access to housing choices, social support networks, and community services, to name a few. Research supports physical and psychosocial benefits of aging-in-place for the individual. Home modifications have the potential to influence the quality of life in a number of positive directions that range from personal mobility to community engagement. Modifications range from minor to significant. Financial resources, contractor interest and expertise, consumer awareness and consumer opportunity affect the degree of change. Increasingly, construction professionals express an interest in learning more about aging-in place. Queries ranged from obtaining a greater understanding of the meaning of the concept, impact of demographic change on housing stock, and increased awareness of universal design features. This paper presents findings from a survey administered to current members of the Canadian Home Builders’ Association – Calgary Regional Office. Within this presentation, we report findings on members understanding of demographic change and the effect of this change on the current and future housing stock. We discuss perceived barriers and benefits of the development of business models to support aging-in-place. Finally, we conclude with discussion of educational support to enhance the understanding of aging-in-place.

Traffic safety at road–rail level crossings using a driving simulator and traffic simulation

Several intelligent transportation systems (ITS) were used with an advanced driving simulator to assess its influence on driving behavior. Three types of ITS interventions were tested: video in vehicle, audio in vehicle, and on-road flashing marker. The results from the driving simulator were inputs for a developed model that used traffic microsimulation (VISSIM 5.4) to assess the safety interventions. Using a driving simulator, 58 participants were required to drive through active and passive crossings with and without an ITS device and in the presence or absence of an approaching train. The effect of changes in driver speed and compliance rate was greater at passive crossings than at active crossings. The slight difference in speed of drivers approaching ITS devices indicated that ITS helped drivers encounter crossings in a safer way. Since the traffic simulation was not able to replicate a dynamic speed change or a probability of stopping that varied depending on ITS safety devices, some modifications were made to the traffic simulation. The results showed that exposure to ITS devices at active crossings did not influence drivers’ behavior significantly according to the traffic performance indicator, such as delay time, number of stops, speed, and stopped delay. However, the results of traffic simulation for passive crossings, where low traffic volumes and low train headway normally occur, showed that ITS devices improved overall traffic performance.

Fatigue capacity of cold-formed steel roof battens under cyclic wind uplift loads

Steel roofs made of thin cold-formed steel roof claddings and battens are widely used in low-rise residential and industrial buildings all around the world. However, they suffer from premature localised pull-through failures in the batten to rafter connections during high wind events. A recent study proposed a suitable design equation for the pull-through failures of thin steel roof battens. However, it was limited to static wind uplift loading. In contrast, most cyclone/storm events produce cyclic wind uplift forces on roofs for a significantly long period, thus causing premature fatigue pull-through failures at lower loads. Therefore, a series of constant amplitude cyclic load tests was conducted on small and full scale roof panels made of a commonly used industrial roof batten to develop their S-N curves. A series of multi-level cyclic tests, including the recently introduced low-high-low (LHL) fatigue loading test, was also undertaken to simulate a design cyclone. Using the S-N curves, the static pull-through design capacity equation was modified to include the effects of fatigue. Applicability of Miner’s rule was evaluated in order to predict the fatigue damage caused by multi-level cyclic tests such as the LHL test, and suitable modifications were made. The combined use of the modified Miner’s law and the S-N curve of roof battens will allow a conservative estimation of the fatigue design capacity of roof battens without conducting the LHL tests simulating a design cyclone. This paper presents the details of this study, and the results.

Ultrasound of paediatric appendicitis and its secondary sonographic signs: Providing a more meaningful finding

Sonography is an important clinical tool in diagnosing appendicitis in children as it can obviate both exposure to potentially harmful ionising radiation from computed tomography scans and the need for unnecessary appendicectomies. This review examines the diagnostic accuracy of ultrasound in the identification of acute appendicitis, with a particular focus on the the utility of secondary sonographic signs as an adjunct or corollary to traditionally examined criteria. These secondary signs can be important in cases where the appendix cannot be identified with ultrasound and a more meaningful finding may be made by incorporating the presence or absence of secondary sonographic signs. There is evidence that integrating these secondary signs into the final ultrasound diagnosis can improve the utility of ultrasound in cases where appendicitis is expected, though there remains some conjecture about whether they play a more important role in negative or positive prediction in the absence of an identifiable appendix.

Clinical tips: Actively supporting customers to make a significant lifestyle change for New Year

We have all made these New Year’s resolutions before ... to be healthier, to eat better, to look after ourselves more, to go to the gym more. Each year, we are adamant we will stick with these resolutions, but deep down, we all know most of us will have given up before February even arrives. So we have put together a few tips to help you actively support your customers to make a significant lifestyle change for the New Year. Healthy eating – it is important for your customers to have realistic expectations. It is all too easy to say they will stop eating junk food, and start ‘eating healthy’. Advising them that it is important to be realistic and starting with a few small measurable goals, such as aiming to eat two servings of fruits or five servings of vegetables each day, will work better in the long run. Small tweaks and modifications can add up to a major change quite quickly...

Feasibility of a stepped wedge cluster RCT and concurrent observational sub-study to evaluate the effects of modified ward night lighting on inpatient fall rates and sleep quality: A protocol for a pilot trial

Background: Falls among hospitalised patients impose a considerable burden on health systems globally and prevention is a priority. Some patient-level interventions have been effective in reducing falls, but others have not. An alternative and promising approach to reducing inpatient falls is through the modification of the hospital physical environment and the night lighting of hospital wards is a leading candidate for investigation. In this pilot trial, we will determine the feasibility of conducting a main trial to evaluate the effects of modified night lighting on inpatient ward level fall rates. We will test also the feasibility of collecting novel forms of patient level data through a concurrent observational sub-study. Methods/design: A stepped wedge, cluster randomised controlled trial will be conducted in six inpatient wards over 14 months in a metropolitan teaching hospital in Brisbane (Australia). The intervention will consist of supplementary night lighting installed across all patient rooms within study wards. The planned placement of luminaires, configurations and spectral characteristics are based on prior published research and pre-trial testing and modification. We will collect data on rates of falls on study wards (falls per 1000 patient days), the proportion of patients who fall once or more, and average length of stay. We will recruit two patients per ward per month to a concurrent observational sub-study aimed at understanding potential impacts on a range of patient sleep and mobility behaviour. The effect on the environment will be monitored with sensors to detect variation in light levels and night-time room activity. We will also collect data on possible patient-level confounders including demographics, pre-admission sleep quality, reported vision, hearing impairment and functional status. Discussion: This pragmatic pilot trial will assess the feasibility of conducting a main trial to investigate the effects of modified night lighting on inpatient fall rates using several new methods previously untested in the context of environmental modifications and patient safety. Pilot data collected through both parts of the trial will be utilised to inform sample size calculations, trial design and final data collection methods for a subsequent main trial.

Economic consideration for reducing hospital presentations among patients with decompensated cirrhosis: not all presentations avoided can be considered equal

Individuals with decompensated cirrhosis and ascites requiring paracentesis utilize exceptionally high levels of hospital resources. Consequently, potential modifications to existing models of healthcare to assist patients in the management of their liver disease and reduce the need for hospital encounters have potential to improve patients’ health and reduce demand on acute hospital services. However, there is a paucity of data examining how much healthcare resources could be re-directed to interventions that prevent hospitalizations without net annual budgetary disadvantage (from the hospital’s perspective). The purpose of this study was to probabilistically examine how much healthcare resourcing could be saved per hospital presentation avoided among this clinical population.

Computation of confined swirling flow using RNG and k-epsilon turbulence models

In this work we numerically model isothermal turbulent swirling flow in a cylindrical burner. Three versions of the RNG k-epsilon model are assessed against performance of the standard k-epsilon model. Sensitivity of numerical predictions to grid refinement, differing convective differencing schemes and choice of (unknown) inlet dissipation rate, were closely scrutinised to ensure accuracy. Particular attention is paid to modelling the inlet conditions to within the range of uncertainty of the experimental data, as model predictions proved to be significantly sensitive to relatively small changes in upstream flow conditions. We also examine the characteristics of the swirl--induced recirculation zone predicted by the models over an extended range of inlet conditions. Our main findings are: - (i) the standard k-epsilon model performed best compared with experiment; - (ii) no one inlet specification can simultaneously optimize the performance of the models considered; - (iii) the RNG models predict both single-cell and double-cell IRZ characteristics, the latter both with and without additional internal stagnation points. The first finding indicates that the examined RNG modifications to the standard k-e model do not result in an improved eddy viscosity based model for the prediction of swirl flows. The second finding suggests that tuning established models for optimal performance in swirl flows a priori is not straightforward. The third finding indicates that the RNG based models exhibit a greater variety of structural behaviour, despite being of the same level of complexity as the standard k-e model. The plausibility of the predicted IRZ features are discussed in terms of known vortex breakdown phenomena.

Automatic wildfire detection and simulation using optical information from unmanned aerial systems

In many parts of the world, uncontrolled fires in sparsely populated areas are a major concern as they can quickly grow into large and destructive conflagrations in short time spans. Detecting these fires has traditionally been a job for trained humans on the ground, or in the air. In many cases, these manned solutions are simply not able to survey the amount of area necessary to maintain sufficient vigilance and coverage. This paper investigates the use of unmanned aerial systems (UAS) for automated wildfire detection. The proposed system uses low-cost, consumer-grade electronics and sensors combined with various airframes to create a system suitable for automatic detection of wildfires. The system employs automatic image processing techniques to analyze captured images and autonomously detect fire-related features such as fire lines, burnt regions, and flammable material. This image recognition algorithm is designed to cope with environmental occlusions such as shadows, smoke and obstructions. Once the fire is identified and classified, it is used to initialize a spatial/temporal fire simulation. This simulation is based on occupancy maps whose fidelity can be varied to include stochastic elements, various types of vegetation, weather conditions, and unique terrain. The simulations can be used to predict the effects of optimized firefighting methods to prevent the future propagation of the fires and greatly reduce time to detection of wildfires, thereby greatly minimizing the ensuing damage. This paper also documents experimental flight tests using a SenseFly Swinglet UAS conducted in Brisbane, Australia as well as modifications for custom UAS.

Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition

Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear. This information is important as Laskowski inhibitors are becoming increasingly used as design templates to develop new protease inhibitors for pharmaceutical applications. In this study, we used the cyclic peptide, sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the inhibitor's sequence and structure relate to its binding kinetics and function. Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants with diverse sequence and backbone modifications, we show that the geometry of the binding loop mainly influences the inhibitor's potency by modulating the association rate, such that variants lacking a favourable conformation show dramatic losses in activity. Additionally, we show that the inhibitor's sequence (including both the binding loop and its scaffolding) influences its potency and selectivity by modulating both the association and the dissociation rates. These findings provide new insights into protease inhibitor function and design that we apply by engineering novel inhibitors for classical serine proteases, trypsin and chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are implicated in various cancers and skin diseases.

Epigenetics Underpinning DNA Damage Repair

Epigenetics is the study of heritable changes in gene expression that are not the result of genetic alterations. These changes include DNA methylation, histone modifications, or indeed microRNA expression. Chromatin is a tightly compacted DNA–protein complex that allows approximately two meters of DNA to be packaged inside a cell, only a few micrometers across. Although the resulting DNA structure is very stable, it is not very amiable to DNA-dependent processes, so mechanisms have to exist to allow processes such as transcription, replication, and DNA repair to occur. This chapter will look at how a cell responds to and deals with genomic instability at the epigenetic level and highlight how critical chromatin remodeling is for correct DNA repair and cell survival following DNA damage. This chapter will initially look at the DNA repair pathways that function in human cells and then at how the repair of DNA damage is controlled by epigenetics.

Epigenetic therapy in lung cancer and mesothelioma

Thoracic malignancies present a considerable global health burden with the incidence and mortality of both lung cancer and malignant pleural mesothelioma (MPM) increasing year on year. Survival rates are poor and treatment options are limited in these cancers. Several epigenetic modifications have been associated with the development of both of these diseases with alterations discriminating between MPM and adenocarcinoma (AC) of the lung. In addition, studies have suggested that epigenetic agents are effective in altering the cellular characteristics of lung and MPM cells in terms of proliferation and migration. Furthermore, it has been demonstrated that epigenetic therapy can alter a pathologically relevant gene expression profile, with one that is more associated with comparative normal tissue. Therefore agents, which target the epi-genomes of lung cancer and MPM, may provide a substantial therapeutic improvement when used in combination with current therapy or indeed benefit when used as a single treatment modality.