Nonlinear Systems in Medicine

Many achievements in medicine have come from applying linear theory to problems. Most current methods of data analysis use linear models, which are based on proportionality between two variables and/or relationships described by linear differential equations. However, nonlinear behavior commonly occurs within human systems due to their complex dynamic nature; this cannot be described adequately by linear models. Nonlinear thinking has grown among physiologists and physicians over the past century, and non-linear system theories are beginning to be applied to assist in interpreting, explaining, and predicting biological phenomena. Chaos theory describes elements manifesting behavior that is extremely sensitive to initial conditions, does not repeat itself and yet is deterministic. Complexity theory goes one step beyond chaos and is attempting to explain complex behavior that emerges within dynamic nonlinear systems. Nonlinear modeling still has not been able to explain all of the complexity present in human systems, and further models still need to be refined and developed. However, nonlinear modeling is helping to explain some system behaviors that linear systems cannot and thus will augment our understanding of the nature of complex dynamic systems within the human body in health and in disease states

Mathematical and mechanical modeling of vaso-occlusion in sickle cell disease

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2007.Includes bibliographical references.Vaso-occlusive crises cause most of the morbidity and mortality associated with sickle cell disease. The proximal causes of these occlusive events are not well understood. The risks and consequences of vaso-occlusion however are clear. Ten percent of sickle cell disease patients will have a stroke by the age of 20. Two thirds of sickle cell disease patients require more than one hospitalization per year for treatment of pain crises. The flow behavior of blood samples from sickle cell patients was studied in an artificial microfluidic environment. This microfluidic environment allowed modulation of the hydrostatic pressure causing flow, the ambient oxygen concentration, and the vascular channel geometry. A range of blood samples was evaluated by selecting specimens with various hematocrits and concentrations of sickle hemoglobin. Velocity profiles were calculated following sudden changes in oxygen concentration. From these profiles, it was possible to create a phase space of vaso-occlusion in the artificial microfluidic environment. This phase space characterizes the environmental conditions in which sickle cell blood will stop flowing within a given interval of time.(cont.) This work is a first step in characterizing the inter-relationships between some of the control parameters governing vaso-occlusion: pressure, oxygen concentration, channel size, hematocrit, and sickle hemoglobin concentration. This artificial device enables a quantification of the effect of a clinical therapy, red blood cell exchange, as performed on an actual sickle cell patient. Additionally, three sample small molecules known to alter rates of sickle hemoglobin polymerization were evaluated for their ability to perturb the tendency of sickle cell blood to stop flowing. These results suggest a possible application of this technique to the diagnosis and monitoring of sickle cell patients as well as to the investigation of new regimens of existing treatments and altogether novel therapies.by John M. Higgins.S.M

Rate Response Assessment from Various Granular VRT Applicators

Variable-rate technology (VRT) adds complexity to application equipment, thereby confounding the assessment of applicator performance. The intent of this investigation was to assess the rate response of various VRT granular applicators: two spinner spreaders (A and B), and two pneumatic applicators (C and D). Variable-rate (VR) tests were conducted to quantify the rate response characteristics (delay and transition times) for the applicators. A sigmoidal function was used to model the rate response for five of the six tests. Applicator A exhibited a linear response during decreasing rate changes. Results indicated that only applicator B demonstrated consistent delay and transition times, enabling the use of a single “look-ahead” time for rate response time correction. Contouring of prescription maps increased the transition times for applicator D by enlarging the adjustment area between management zones. Rate changes were quicker for the two newer VR control systems, signifying advancement in hydraulic control valve technology. This research illustrates the need for standard testing protocols for VRT systems to help guide VRT software developers, equipment manufacturers, and end users

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: Systematic review and meta-regression

Objective: To assess the impact of inadequate water and sanitation on diarrhoeal disease in low- and middle-income settings. Methods: The search strategy used Cochrane Library, MEDLINE & PubMed, Global Health, Embase and BIOSIS supplemented by screening of reference lists from previously published systematic reviews, to identify studies reporting on interventions examining the effect of drinking water and sanitation improvements in low- and middle-income settings published between 1970 and May 2013. Studies including randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined were eligible. Risk of bias was assessed using a modified Ottawa-Newcastle scale. Study results were combined using meta-analysis and meta-regression to derive overall and intervention-specific risk estimates. Results: Of 6819 records identified for drinking water, 61 studies met the inclusion criteria, and of 12 515 records identified for sanitation, 11 studies were included. Overall, improvements in drinking water and sanitation were associated with decreased risks of diarrhoea. Specific improvements, such as the use of water filters, provision of high-quality piped water and sewer connections, were associated with greater reductions in diarrhoea compared with other interventions. Conclusions: The results show that inadequate water and sanitation are associated with considerable risks of diarrhoeal disease and that there are notable differences in illness reduction according to the type of improved water and sanitation implemented

Gender Differences in Demographic and Clinical Correlates among Veterans with Musculoskeletal Disorders

Background Studies suggest that women may be at greater risk for developing chronic pain and pain-related disability. Methods Because musculoskeletal disorders (MSD) are the most frequently endorsed painful conditions among veterans, we sought to characterize gender differences in sociodemographic and clinical correlates among veterans upon entry into Veterans Health Administration's Musculoskeletal Disorders Cohort (n = 4,128,008). Results Women were more likely to be younger, Black, unmarried, and veterans of recent conflicts. In analyses adjusted for gender differences in sociodemographics, women were more likely to have diagnoses of fibromyalgia, temporomandibular disorders, and neck pain. Almost one in five women (19.4%) had more than one MSD diagnosis, compared with 15.7% of men; this higher risk of MSD multimorbidity remained in adjusted analyses. Adjusting for sociodemographics, women with MSD were more likely to have migraine headache and depressive, anxiety, and bipolar disorders. Women had lower odds of cardiovascular diseases, substance use disorders, and several MSDs, including back pain conditions. Men were more likely to report “no pain” on the pain intensity Numeric Rating Scale, whereas more women (41%) than men (34%) reported moderate to severe pain (Numeric Rating Scale 4+). Conclusions Because women veterans are more likely to have conditions such as fibromyalgia and mental health conditions, along with greater pain intensity in the setting of MSD, women-specific pain services may be needed