A three-dimensional mathematical model of the thoracolumbar fascia and an estimate of its biomechanical effect.

The thoracolumbar fascia (TLF) provides a means of attachment to the lumbar spine for several muscles including the transverse abdominis, and parts of the latissimus dorsi and internal oblique muscles. Previous biomechanical models of the lumbar spine either tend to omit the TLF on the assumption that its contribution would be negligible or incorporate only part of the TLF. Here, a three-dimensional model of the posterior and middle layers of the TLF is presented to enable its action to be included in future three-dimensional models of the spine. It is used illustratively to estimate the biomechanical influence of this structure on the lumbar spine. The formulation of the model allows the lines of action of the fibres comprising the fascia to be calculated for any posture whilst ensuring that anatomical constraints are satisfied. Application of the model suggests that the TLF produces moments primarily in flexion and extension. The simulated results demonstrate that the abdominal muscles, acting via the TLF, are capable of contributing extension moments comparable to those produced by other smaller muscles associated with the lumbar spine.

Sequential monitoring of hospital adverse events when control charts fail: the example of fall injuries in hospitals.

OBJECTIVE: To evaluate methods for monitoring monthly aggregated hospital adverse event data that display clustering, non-linear trends and possible autocorrelation. DESIGN: Retrospective audit. SETTING: The Northern Hospital, Melbourne, Australia. PARTICIPANTS: 171,059 patients admitted between January 2001 and December 2006. MEASUREMENTS: The analysis is illustrated with 72 months of patient fall injury data using a modified Shewhart U control chart, and charts derived from a quasi-Poisson generalised linear model (GLM) and a generalised additive mixed model (GAMM) that included an approximate upper control limit. RESULTS: The data were overdispersed and displayed a downward trend and possible autocorrelation. The downward trend was followed by a predictable period after December 2003. The GLM-estimated incidence rate ratio was 0.98 (95% CI 0.98 to 0.99) per month. The GAMM-fitted count fell from 12.67 (95% CI 10.05 to 15.97) in January 2001 to 5.23 (95% CI 3.82 to 7.15) in December 2006 (p<0.001). The corresponding values for the GLM were 11.9 and 3.94. Residual plots suggested that the GLM underestimated the rate at the beginning and end of the series and overestimated it in the middle. The data suggested a more rapid rate fall before 2004 and a steady state thereafter, a pattern reflected in the GAMM chart. The approximate upper two-sigma equivalent control limit in the GLM and GAMM charts identified 2 months that showed possible special-cause variation. CONCLUSION: Charts based on GAMM analysis are a suitable alternative to Shewhart U control charts with these data.

Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.

In an open-label sequential cohort study, we compared gastrointestinal (GI) disturbances and plasma tafenoquine concentrations after administration of single-dose (400mg daily x 3 days; n=76 males, 11 females) and split-dose (200 mg twice daily x 3 days; n=73 males, 13 females) tafenoquine regimens in healthy Australian Defence Force volunteers for post-exposure malaria prophylaxis. The female and male volunteers had comparable demographic characteristics (age, weight, height) in the single- and split-dose treatment groups. GI disturbances were generally mild and self-limiting for both groups. The frequency of nausea and abdominal distress was over two-fold higher in females than in males for both treatment groups. Reporting of GI disturbances in the single-dose group differed significantly between males and females, but this gender difference was not seen for the split-dose group. In those volunteers who experienced GI disturbances, the mean plasma tafenoquine concentrations 12 h after the last dose of tafenoquine were approximately 1.3-fold higher in females than in males (means+/-SD: 737+/-118 ng/ml vs. 581+/-113 ng/ml). These preliminary findings suggest that further studies are required in a larger number of females to determine whether there is a need to reduce the dose of tafenoquine to minimise GI disturbances in females.

Ross River virus disease clusters and spatial relationship with mosquito biting exposure in Redland Shire, southern Queensland, Australia.

The spatial heterogeneity in the risk of Ross River virus (family Togaviridae, genus Alphavirus, RRV) disease, the most common mosquito-borne disease in Australia, was examined in Redland Shire in southern Queensland, Australia. Disease cases, complaints from residents of intense mosquito biting exposure, and human population data were mapped using a geographic information system. Surface maps of RRV disease age-sex standardized morbidity ratios and mosquito biting complaint morbidity ratios were created. To determine whether there was significant spatial variation in disease and complaint patterns, a spatial scan analysis method was used to test whether the number of cases and complaints was distributed according to underlying population at risk. Several noncontiguous areas in proximity to productive saline water habitats of Aedes vigilax (Skuse), a recognized vector of RRV, had higher than expected numbers of RRV disease cases and complaints. Disease rates in human populations in areas which had high numbers of adult Ae. vigilax in carbon dioxide- and octenol-baited light traps were up to 2.9 times those in areas that rarely had high numbers of mosquitoes. It was estimated that targeted control of adult Ae. vigilax in these high-risk areas could potentially reduce the RRV disease incidence by an average of 13.6%. Spatial correlation was found between RRV disease risk and complaints from residents of mosquito biting. Based on historical patterns of RRV transmission throughout Redland Shire and estimated future human population growth in areas with higher than average RRV disease incidence, it was estimated that RRV incidence rates will increase by 8% between 2001 and 2021. The use of arbitrary administrative areas that ranged in size from 4.6 to 318.3 km2 has the potential to mask any small scale heterogeneity in disease patterns. With the availability of georeferenced data sets and high-resolution imagery, it is becoming more feasible to undertake spatial analyses at relatively small scales.

Analysis of Barmah Forest virus disease activity in Queensland, Australia, 1993-2003: identification of a large, isolated outbreak of disease.

Barmah Forest virus (BFV) disease is the second most common mosquito-borne disease in Australia. Although the majority of notifications are received from Queensland, little is known about the distribution of the disease within the state, or the important mosquito vectors and nonhuman vertebrate hosts. We conducted a retrospective statistical analysis of the notifications received from Queensland residents from 1993 to 2003 to establish long-term local incidence rates and to identify disease outbreaks. In total, 4,544 notifications were received over the 10-yr period. Disease reporting peaked in autumn, although the peak transmission season encompassed both summer and autumn. Long-term standardized incidence rates for summer/autumn and winter/spring varied across the state, showing positive spatial autocorrelation in both 6-mo periods. Although 15 instances of increased disease activity were identified, only one major disease outbreak affecting eight contiguous local government areas was detected in summer/autumn 2002/2003. This outbreak contained 297 cases, 115 more than would be expected over this period. The factors important to this outbreak are unknown and require further investigation. Although the incidence rates for BFV disease are lower than Ross River virus disease, the most reported mosquito-borne disease in Australia, several factors indicate that this virus should be considered an important public health risk in Queensland. These include consistent endemic transmission, apparent underreporting of the disease, and the potential for outbreaks in major population centers.

Costs to the patient for seeking malaria care in Myanmar.

This study investigates the costs incurred by patients diagnosed with uncomplicated malaria at a formal rural health facility in Myanmar. A cross-sectional survey of 410 patients indicated that the majority of patients were male (89.3%), married (84.6%) and the head of their family (80.2%); this spectrum reflected the deliberate selection of persons for whom relatively accurate costing was feasible. The average total costs incurred for an episode of malaria was kyats 173.58 (95% CI = 166.13-181.02). with the highest cost contribution being the loss of earnings due to absence from work (mean = kyats 135.05; 95% CI = 128.14-141.96). Total costs to the patient per episode were, on the average, equivalent to 4.2 days of per capita economic output indicating that malaria imposes a significant financial burden on the patient even though medical services and treatment are provided free of charge. Variables significantly positively associated with patient cost included the duration of illness (P < 0.001), income of the patient (P < 0.001), presence of accompanying person at the health facility (P < 0.001) and being a farmer (P = 0.026). The results of this study highlight the importance of using confirmatory diagnosis in rural settings to minimize the financial burden of malaria to the patient and family.

Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naïve hosts.

Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host-parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naïve hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.

The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling.

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections. We explore 3 switching mechanisms: ordered, random and uncoupled switching. We show that if var genes switch on and off independently at variable rates through the repertoire a chronic clinical infection is predicted. The fastest switching-on rate that produces a chronic infection is 0.03% per generation. The model predicts that non-variant specific immunity plays an important role in reducing disease severity. This work illustrates the complex relationship between the malaria parasite and its host and shows that var gene switching at rates substantially slower than 2% are essential for parasite survival.

Performance appraisal of rapid on-site malaria diagnosis (ICT malaria Pf/Pv test) in relation to human resources at village level in Myanmar.

Logistic, economic and technical factors limit rapid access to microscopic confirmation of symptomatic diagnosis of malaria in many rural areas in endemic countries such as Myanmar. A study was conducted to evaluate a rapid on-site immunochromatographic test (ICT Malaria Pf/Pv) for detection of Plasmodium falciparum and P. vivax in two villages in the Taikkyi region of Myanmar. The ICT Malaria tests were performed by a volunteer health worker (VHW) in Yae-Aye-San village and by a professionally trained midwife (MW) in Kankone village. A total of 1000 symptomatic patients participated in the study by providing blood samples for an ICT test and for microscopy. The ICT performance indices, relative to microscopy, were better for the trained MW compared with the less experienced VHW. For P. falciparum and/or P. vivax infections, the sensitivities were 82.7% for the VHW compared with 93.7% for the MW. For P. falciparum infections, the sensitivities were 82.2% for the VHW and 91.3% for the MW, while the corresponding values for P. vivax infections were 66.7 and 79%, respectively. Although the test kit appeared to perform better in more experienced hands, this study questions whether this difference is related to the use of the ICT Malaria Pf/Pv test kit, or related to other factors such as differences in the quality of blood slides prepared by the VHW and MW for microscopic examination. Overall, the results suggest that a rapid diagnostic assay such as the ICT Malaria Pf/Pv test kit can be used in rural settings by relatively inexperienced persons, such as VHWs, with a reasonable degree of sensitivity, thus providing on-site confirmation of symptomatic diagnosis of malaria.

Modelling the line of action for the oblique abdominal muscles using an elliptical torso model.

When modelling the line of action of a muscle, anatomical considerations must be included if the model is to realistically mimic the muscle behaviour. The internal and external oblique muscles are examples of muscles that do not follow a straight line between origin and insertion, instead having to wrap around the torso. A model is presented which describes the shape of the torso using a right elliptical cylinder of varying dimensions. The muscle lines of action are then calculated based on this underlying torso shape. The model has been successfully fitted to the data reported by Stokes and Gardner-Morse (Journal of Biomechanics 32(3) (1999) 311). When compared to a linear model, the use of the torso model results in a 15% increase in the axial twist moment, and decreases in the lateral bend and extension moments (5% and 2%, respectively), able to be generated by the internal and external oblique muscles combined in upright stance. These differences become larger (up to 37%) when the torso is flexed, extended or twisted. The structure of the torso model allows it to be used to model any posture without significant increases in the overall model complexity.

Child-Pugh class, nutritional indicators and early liver transplant outcomes.

BACKGROUND/AIMS: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). METHODOLOGY: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. RESULTS: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found for length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. CONCLUSIONS: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.

Time of treatment influences the appearance of drug-resistant parasites in Plasmodium falciparum infections.

A deterministic mathematical model which predicts the probability of developing a new drug-resistant parasite population within the human host is reported. The model incorporates the host's specific antibody response to PfEMP1, and also investigates the influence of chemotherapy on the probability of developing a viable drug-resistant parasite population within the host. Results indicate that early treatment, and a high antibody threshold coupled with a long lag time between antibody stimulation and activity, are risk factors which increase the likelihood of developing a viable drug-resistant parasite population. High parasite mutation rates and fast PfEMP1 var gene switching are also identified as risk factors. The model output allows the relative importance of the various risk factors as well as the relationships between them to be established, thereby increasing the understanding of the conditions which favour the development of a new drug-resistant parasite population.

Kinematics and movement sequencing during flexion of the lumbar spine.

OBJECTIVES: This study investigated the sequence of intervertebral joint movements and range of motion during three tasks involving lumbar flexion. DESIGN: Position sensors were used to measure position and rotation of lumbar vertebrae during unconstrained flexion. BACKGROUND: In the development of mathematical models, numerous assumptions need to be made. Few studies have attempted to assess the validity of the assumptions regarding kinematics in models of the lumbar spine. METHODS: Position sensors were attached to the skin overlying the lumbar vertebrae of 14 volunteers. Volunteers performed three flexion tasks; unconstrained flexion from upright standing, with and without a mass of 5 kg held close to the body, and the transition from upright standing to a seated position. RESULTS: Four definitive movement sequences were identified for those subjects with consistency between replicates; 'top down' motion (where the top of the lumbar spine starts to move first and the bottom moves last), 'bottom up' (where the bottom of the lumbar spine moves first and the top moves last), 'all together' (where all segments commence movement together), and 'middle last' (where the middle segments of the lumbar spine are last to commence movement). Subjects not fitting one of these sequences were categorised into a miscellaneous group. Only two subjects exhibited the same sequence for each of the three tasks, while other subjects exhibited two or three different sequences for the three tasks, or showed a lack of consistency for one of the tasks. CONCLUSIONS: The results from this study indicate that there is no single movement sequence exhibited by the sample population. RELEVANCE: Incorrect assumptions which are incorporated into mathematical models have the potential to influence model output. Given that output from spinal models is often used to assess ergonomic issues such as safe lifting loads, validation of the assumptions is essential.

Difficulties in estimating muscle forces from muscle cross-sectional area. An example using the psoas major muscle.

Most biomechanical models use muscle cross-sectional area (CSA) as an indicator of maximum isometric muscle force. In general, there are multiple estimates of CSA for the same muscle. For example, numerous studies have estimated the CSA of the psoas major muscle using different subject populations and positions. However, few studies have combined the available information to obtain an overall estimate of CSA or investigated the effect different subject characteristics may have on CSA. In the present update, nine studies that reported psoas major CSA or physiologic CSA were compared with respect to subject characteristics, methodology, and results. Corrections to cadaveric data were made to adjust physiologic CSA to CSA. Comparison of reported values for living subjects indicated that females have smaller mean CSA than males for the psoas major muscle and that body size does not significantly influence muscle CSA in males. Areas derived from cadaveric data were smaller than similar studies on living subjects, possibly because of subject age, removal of tendinous and fatty components of fascicles, and lack of detailed data for fascicle angles in the supine position. Results indicate that researchers who use muscle CSA in biomechanical models should carefully assess the appropriateness of the data used, particularly in relation to potential sex differences and the influence of postural changes on CSA.

Field epidemiological studies on malaria in a low endemic area in the Philippines.

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.

A model for predicting the transmission rate of malaria from serological data.

A model is developed to estimate the duration for which malaria antibody levels in the blood remain high in a closed population. This estimate can be used to calculate the transmission rate within a region, in conjunction with the serological information contained in the population. The model is used on data obtained from a study of malaria in the Philippines and shows excellent agreement. It is subsequently utilised for predictions and seems to be an appropriate vehicle for this purpose.