A Spoonful of Math Helps the Medicine Go Down: An Illustration of How Healthcare can Benefit from Mathematical Modeling and Analysis

<p>Abstract</p> <p>Objectives</p> <p>A recent joint report from the Institute of Medicine and the National Academy of Engineering, highlights the benefits of--indeed, the need for--mathematical analysis of healthcare delivery. Tools for such analysis have been developed over decades by researchers in Operations Research (OR). An OR perspective typically frames a complex problem in terms of its essential mathematical structure. This article illustrates the use and value of the tools of operations research in healthcare. It reviews one OR tool, queueing theory, and provides an illustration involving a hypothetical drug treatment facility.</p> <p>Method</p> <p>Queueing Theory (QT) is the study of waiting lines. The theory is useful in that it provides solutions to problems of waiting and its relationship to key characteristics of healthcare systems. More generally, it illustrates the strengths of modeling in healthcare and service delivery.</p> <p>Queueing theory offers insights that initially may be hidden. For example, a queueing model allows one to incorporate randomness, which is inherent in the actual system, into the mathematical analysis. As a result of this randomness, these systems often perform much worse than one might have guessed based on deterministic conditions. Poor performance is reflected in longer lines, longer waits, and lower levels of server utilization.</p> <p>As an illustration, we specify a queueing model of a representative drug treatment facility. The analysis of this model provides mathematical expressions for some of the key performance measures, such as average waiting time for admission.</p> <p>Results</p> <p>We calculate average occupancy in the facility and its relationship to system characteristics. For example, when the facility has 28 beds, the average wait for admission is 4 days. We also explore the relationship between arrival rate at the facility, the capacity of the facility, and waiting times.</p> <p>Conclusions</p> <p>One key aspect of the healthcare system is its complexity, and policy makers want to design and reform the system in a way that affects competing goals. OR methodologies, particularly queueing theory, can be very useful in gaining deeper understanding of this complexity and exploring the potential effects of proposed changes on the system without making any actual changes.</p

Neural Correlates of Visual Motion Prediction

Predicting the trajectories of moving objects in our surroundings is important for many life scenarios, such as driving, walking, reaching, hunting and combat. We determined human subjects’ performance and task-related brain activity in a motion trajectory prediction task. The task required spatial and motion working memory as well as the ability to extrapolate motion information in time to predict future object locations. We showed that the neural circuits associated with motion prediction included frontal, parietal and insular cortex, as well as the thalamus and the visual cortex. Interestingly, deactivation of many of these regions seemed to be more closely related to task performance. The differential activity during motion prediction vs. direct observation was also correlated with task performance. The neural networks involved in our visual motion prediction task are significantly different from those that underlie visual motion memory and imagery. Our results set the stage for the examination of the effects of deficiencies in these networks, such as those caused by aging and mental disorders, on visual motion prediction and its consequences on mobility related daily activities

Salmonella bongori provides insights into the evolution of the Salmonellae.

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC.We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups and the MRC for their support of GF, KSR and GNS. MCF, GCL, TRC, HSS, GSV, MS, NKP, RAK, JP, GD and NRT were supported by Wellcome Trust grant 076964 and MICROME, an EU Framework Programme 7 Collaborative Project, Grant Agreement Number 222886-2. Work was also supported by Grant ADI-08/2006 from Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and The World Bank, and grant 1100092 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). CJB was supported by fellowships from CONICYT (21080373 and AT-24091015)

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

THE EFFECT OF ENERGY SHOTS ON HAND STEADINESS AND REACTION TIME

Bert H. Jacobson, FACSM, Patricia P. Hughes, Eric Conchola & Garrett Hester Health and Human Performance Laboratory, Oklahoma State University Stillwater, Oklahoma Energy drinks (EDs) and energy shots (ES) have become popular because they are purported to promote vitality, energy, and enhanced physical performance. PURPOSE: The purpose of this study was to assess the effect of a commercial energy shot on hand steadiness and reaction time. METHODS: Following IRB approval, 14 college-aged males and 18 females were tested for hand steadiness by holding a stylus in three descending diameter holes (7.92mm, 4.75mm, 2.77mm) for 20s each with a 30s rest between sets. Frequency of stylus to edge hits were measured and recorded. Reaction time was measured using a computerized program. The task included pressing the mouse button at the instance a light switched from red to green. Five trials of five repetitions were given to each subject. Following pre-testing subjects were randomly divided into an experimental group and a control group. The experimental group was given a commercial ES (57 ml) and the control was given a placebo. Following 30 min of inactive resting subjects were tested again. RESULTS: One way ANOVAs indicated that the ES group scored significantly (ppCONCLUSION: It is possible that reaction time improvement could be beneficial in sports that require quick, reflexive movement. However, the potential adverse psychological and physiological effects warrant discretionary use of such products