THE MULTIPLE LOCATION TIME WEIGHTED INDEX: USING PATIENT ACTIVITY SPACES TO CALCULATE PRIMARY CARE SERVICE AREAS

Geographic health planning analyses, such as service area calculations, are hampered by a lack of patient-specific geographic data. Using the limited patient address information in patient management systems, planners analyze patient origin based on home address. But activity space research done sparingly in public health and extensively in non-health related arenas uses multiple addresses per person when analyzing accessibility. Also, health care access research has shown that there are many non-geographic factors that influence choice of provider. Most planning methods, however, overlook non-geographic factors influencing choice of provider, and the limited data mean the analyses can only be related to home address. This research attempted to determine to what extent geography plays a part in patient choice of provider and to determine if activity space data can be used to calculate service areas for primary care providers. During Spring 2008, a convenience sample of 384 patients of a locally-funded Community Health Center in Houston, Texas, completed a survey that asked about what factors are important when he or she selects a health care provider. A subset of this group (336) also completed an activity space log that captured location and time data on the places where the patient regularly goes. Survey results indicate that for this patient population, geography plays a role in their choice of health care provider, but it is not the most important reason for choosing a provider. Other factors for choosing a health care provider such as the provider offering “free or low cost visits”, meeting “all of the patient’s health care needs”, and seeing “the patient quickly” were all ranked higher than geographic reasons. Analysis of the patient activity locations shows that activity spaces can be used to create service areas for a single primary care provider. Weighted activity-space-based service areas have the potential to include more patients in the service area since more than one location per patient is used. Further analysis of the logs shows that a reduced set of locations by time and type could be used for this methodology, facilitating ongoing data collection for activity-space-based planning efforts.

Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.

Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID) mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained "template-independent" sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice) is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.

Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields.

The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network.

Lobe specific Ca2+-calmodulin nano-domain in neuronal spines: a single molecule level analysis.

Calmodulin (CaM) is a ubiquitous Ca(2+) buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca(2+)-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca(2+)-CaM-dependent enzymes: Ca(2+)/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca(2+) and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca(2+) ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca(2+) and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca(2+) signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca(2+)-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca(2+) channels, and to the microscopic injection rate of Ca(2+) ions. We also demonstrate that Ca(2+) saturation takes place via two different pathways depending on the Ca(2+) injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca(2+) sensors that can differentially transduce Ca(2+) influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca(2+)-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity.

Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection.

Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID) mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained "template-independent" sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice) is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.

The multiple location time weighted index: Using patient activity spaces to calculate primary care service areas

Geographic health planning analyses, such as service area calculations, are hampered by a lack of patient-specific geographic data. Using the limited patient address information in patient management systems, planners analyze patient origin based on home address. But activity space research done sparingly in public health and extensively in non-health related arenas uses multiple addresses per person when analyzing accessibility. Also, health care access research has shown that there are many non-geographic factors that influence choice of provider. Most planning methods, however, overlook non-geographic factors influencing choice of provider, and the limited data mean the analyses can only be related to home address. This research attempted to determine to what extent geography plays a part in patient choice of provider and to determine if activity space data can be used to calculate service areas for primary care providers. ^ During Spring 2008, a convenience sample of 384 patients of a locally-funded Community Health Center in Houston, Texas, completed a survey that asked about what factors are important when he or she selects a health care provider. A subset of this group (336) also completed an activity space log that captured location and time data on the places where the patient regularly goes. ^ Survey results indicate that for this patient population, geography plays a role in their choice of health care provider, but it is not the most important reason for choosing a provider. Other factors for choosing a health care provider such as the provider offering "free or low cost visits", meeting "all of the patient's health care needs", and seeing "the patient quickly" were all ranked higher than geographic reasons. ^ Analysis of the patient activity locations shows that activity spaces can be used to create service areas for a single primary care provider. Weighted activity-space-based service areas have the potential to include more patients in the service area since more than one location per patient is used. Further analysis of the logs shows that a reduced set of locations by time and type could be used for this methodology, facilitating ongoing data collection for activity-space-based planning efforts. ^

Cost analysis of opt-in consent procedures for the Texas statewide immunization information system, ImmTrac

Background. Childhood immunization programs have dramatically reduced the morbidity and mortality associated with vaccine-preventable diseases. Proper documentation of immunizations that have been administered is essential to prevent duplicate immunization of children. To help improve documentation, immunization information systems (IISs) have been developed. IISs are comprehensive repositories of immunization information for children residing within a geographic region. The two models for participation in an IIS are voluntary inclusion, or "opt-in," and voluntary exclusion, or "opt-out." In an opt-in system, consent must be obtained for each participant, conversely, in an opt-out IIS, all children are included unless procedures to exclude the child are completed. Consent requirements for participation vary by state; the Texas IIS, ImmTrac, is an opt-in system.^ Objectives. The specific objectives are to: (1) Evaluate the variance among the time and costs associated with collecting ImmTrac consent at public and private birthing hospitals in the Greater Houston area; (2) Estimate the total costs associated with collecting ImmTrac consent at selected public and private birthing hospitals in the Greater Houston area; (3) Describe the alternative opt-out process for collecting ImmTrac consent at birth and discuss the associated cost savings relative to an opt-in system.^ Methods. Existing time-motion studies (n=281) conducted between October, 2006 and August, 2007 at 8 birthing hospitals in the Greater Houston area were used to assess the time and costs associated with obtaining ImmTrac consent at birth. All data analyzed are deidentified and contain no personal information. Variations in time and costs at each location were assessed and total costs per child and costs per year were estimated. The cost of an alternative opt-out system was also calculated.^ Results. The median time required by birth registrars to complete consent procedures varied from 72-285 seconds per child. The annual costs associated with obtaining consent for 388,285 newborns in ImmTrac's opt-in consent process were estimated at $702,000. The corresponding costs of the proposed opt-out system were estimated to total $194,000 per year. ^ Conclusions. Substantial variation in the time and costs associated with completion of ImmTrac consent procedures were observed. Changing to an opt-out system for participation could represent significant cost savings. ^

Use of light intensity, temperature, and humidity to verify exposure location

Research studies on the association between exposures to air contaminants and disease frequently use worn dosimeters to measure the concentration of the contaminant of interest. But investigation of exposure determinants requires additional knowledge beyond concentration, i.e., knowledge about personal activity such as whether the exposure occurred in a building or outdoors. Current studies frequently depend upon manual activity logging to record location. This study's purpose was to evaluate the use of a worn data logger recording three environmental parameters—temperature, humidity, and light intensity—as well as time of day, to determine indoor or outdoor location, with an ultimate aim of eliminating the need to manually log location or at least providing a method to verify such logs. For this study, data collection was limited to a single geographical area (Houston, Texas metropolitan area) during a single season (winter) using a HOBO H8 four-channel data logger. Data for development of a Location Model were collected using the logger for deliberate sampling of programmed activities in outdoor, building, and vehicle locations at various times of day. The Model was developed by analyzing the distributions of environmental parameters by location and time to establish a prioritized set of cut points for assessing locations. The final Model consisted of four "processors" that varied these priorities and cut points. Data to evaluate the Model were collected by wearing the logger during "typical days" while maintaining a location log. The Model was tested by feeding the typical day data into each processor and generating assessed locations for each record. These assessed locations were then compared with true locations recorded in the manual log to determine accurate versus erroneous assessments. The utility of each processor was evaluated by calculating overall error rates across all times of day, and calculating individual error rates by time of day. Unfortunately, the error rates were large, such that there would be no benefit in using the Model. Another analysis in which assessed locations were classified as either indoor (including both building and vehicle) or outdoor yielded slightly lower error rates that still precluded any benefit of the Model's use.^

A descriptive analysis of the consumers at farm stands outside WIC clinics

Because fruit and vegetable intake remains low in low-income populations, the attention of public health researchers has focused on different strategies to reach this population. One possible method of reaching low income populations is through government food assistance programs like the WIC's Farmers Market Nutrition Program (FMNP). This program provides vouchers to WIC recipients that are redeemable only at farmers' markets. In the summer of 2010, two farm stands near WIC clinics in Austin were surveyed in order to establish socio-demographic characteristics of the clientele of the markets. The overall purpose of this pilot study was to describe the clientele of the markets and to examine associations between food insecurity, acculturation, socio-demographic factors, and farmers' market participants' fruit and vegetable intake. The sample was a convenience sample of farmers' market customers. One hundred study participants completed self-administered surveys. Independent t-tests were used to explore the differences in means of fruit and vegetable intake according to acculturation and food insecurity levels. The overall mean (SD) of daily fruit and vegetable intake was 4.20±2.69 for customers of both markets. Significant differences were reported between the two markets in overall fruit and vegetable intake and specifically in the following: 100% juice (P=.023), fruit consumption (P=.028), green salad (P=.003), and salsa (P=.044). The differences showed that customers at the market in a more busy location were on average reporting eating more fruits and vegetables than customers at another market that was located in a more secluded location. When examined by level of food security, individuals who were more food secure consumed more fruit (P=.016). When examined by level of acculturation, the overall fruit and vegetable intake was not significantly different between levels of acculturation. The overall findings in this report suggest that the population at these markets consists of individuals who are food insecure and on government assistance programs. While there were no significant differences between fruit and vegetable intake, acculturation and food insecurity, this report suggests the need for culturally tailored interventions that serve the Hispanic population and would assist this population to become more food secure.^

Pre-pregnancy obesity on the border and pregnancy complications: A secondary analysis comparing post-natal adult women in Matamoros, Mexico and Cameron County, Texas

Obesity during pregnancy is a serious health concern which has been associated with many adverse health outcomes for both the mother and the infant. In addition, data on the prevalence of obesity and its effects on pregnant women living in the border region are limited. This goal of this study was to examine the prevalence of preconception obesity among women living on each side of the Brownsville-Matamoros border who have just given birth, the relationship between obesity and pregnancy complications for the total population, and these associations by location. Study participants were drawn from a sample (n=947) from the Brownsville-Matamoros Sister City Project which included women from 10 border region hospitals (6 in Matamoros, 4 in Cameron County) who were recruited based on hospital log records indicating they had given birth to a live infant. De-identified data from verbal questionnaires administered within twenty-four hours after birth were analyzed to determine prevalence of preconception obesity on both sides of the border, and associated pregnancy outcomes for women residing in the United States and those in Mexico. Participants with missing height or weight data were excluded from analyses in this study, resulting in a final sample of 727 women. Significant associations were found between pre-pregnancy obesity and adverse pregnancy outcomes (OR=1.85, CI=1.30–2.64), hypertensive conditions (OR=2.76, CI=1.72–4.43), and macrosomia (OR=6.77, CI=1.13–40.57) using the total sample. Comparisons between the United States and Mexico sides of the border showed differences; associations between preconception obesity and adverse pregnancy outcomes were marginally significant among women in the United States (p=0.05), but failed to reach significance within this group for each individual complication. However, significant associations were found between obesity and preeclampsia (OR=3.61, CI=2.14–6.10), as well as obesity and the presence of one or more adverse pregnancy outcome (OR=2.29, CI=1.30–4.02), among women in Mexico. The results from this analysis provide new information specific to women on the Texas and Mexico border, a region that had not previously been studied. These significant associations between preconception obesity and adverse birth outcomes indicate that efforts to prevent obesity should focus on women of childbearing age, especially in Mexico.^

Are anatomic brain locations important in determining the clinical outcomes in acute ischemic stroke? --- An exploratory analysis of the NINDS Stroke Trial data

Background and purpose. Brain lesions in acute ischemic stroke measured by imaging tools provide important clinical information for diagnosis and final infarct volume has been considered as a potential surrogate marker for clinical outcomes. Strong correlations have been found between lesion volume and clinical outcomes in the NINDS t-PA Stroke Trial but little has been published about lesion location and clinical outcomes. Studies of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial data found the direction of the t-PA treatment effect on a decrease in CT lesion volume was consistent with the observed clinical effects at 3 months, but measure of t-PA treatment benefits using CT lesion volumes showed a diminished statistical significance, as compared to using clinical scales. ^ Methods. We used the global test to evaluate the hypothesis that lesion locations were strongly associated with clinical outcomes within each treatment group at 3 months after stroke. The anatomic locations of CT scans were used for analysis. We also assessed the effect of t-PA on lesion location using a global statistical test. ^ Results. In the t-PA group, patients with frontal lesions had larger infarct volumes and worse NIHSS score at 3 months after stroke. The clinical status of patients with frontal lesions in t-PA group was less likely to be affected by lesion volume, as compared to those who had no frontal lesions in at 3 months. For patients within the placebo group, both brain stem and internal capsule locations were significantly associated with a lower odd of having favorable outcomes at 3 months. Using a global test we could not detect a significant effect of t-PA treatment on lesion location although differences between two treatment groups in the proportion of lesion findings in each location were found. ^ Conclusions. Frontal, brain stem, and internal capsule locations were significantly related to clinical status at 3 months after stroke onset. We detect no significant t-PA effect on all 9 locations although proportion of lesion findings in differed among locations between the two treatment groups.^

Retrospective analysis of Methicillin-Resistant Staphylococcus Aureus (MRSA) skin and Soft-Tissue Infections (SSTI) in a university hospital emergency department (ED)

Study Objective: Identify the most frequent risk factors of Community Acquired-MRSA (CA-MRSA) Skin and Soft-tissue Infections (SSTIs) using a case series of patients and characterize them by age, race/ethnicity, gender, abscess location, druguse and intravenous drug-user (IVDU), underlying medical conditions, homelessness, treatment resistance, sepsis, those whose last healthcare visit was within the last 12 months, and describe the susceptibility pattern from this central Texas population that have come into the University Medical Center Brackenridge (UMCB) Emergency Department (ED). ^ Methods: This study was a retrospective case-series medical record review involving a convenience sample of patients in 2007 from an urban public hospital's ED in Texas that had a SSTI that tested positive for MRSA. All positive MRSA cultures underwent susceptibility testing to determine antibiotic resistance. The demographic and clinical variables that were independently associated with MRSA were determined by univariate and multivariate analysis using logistic regression to calculate odds ratios (OR), 95% confidence intervals, and significance (p≤ 0.05). ^ Results: In 2007, there were 857 positive MRSA cultures. The demographics were: males 60% and females 40%, with the average age of 36.2 (std. dev. =13) the study population consisted of non-Hispanic white (42%), Hispanics (38%), and non-Hispanic black (18.8%). Possible risk factors addressed included using recreational drugs (not including IVDU) (27%) homelessness (13%), diabetes status (12.6%) or having an infectious disease, and IVDU (10%). The most frequent abscess location was the leg (26.6%), followed by the arm and torso (both 13.7%). Eighty-three percent of patients had one prominent susceptibility pattern that had a susceptibility rate for the following antibiotics: trimethoprim/sulfamethoxazole (TMP-SMX) and vancomycin had 100%, gentamicin 99%, clindamycin 96%, tetracycline 96%, and erythromycin 56%. ^ Conclusion: The ED is becoming an important area for disease transmission between the sterile hospital environment and the outside environment. As always, it is important to further research in the ED in an effort to better understand MRSA transmission and antibiotic resistance, as well as to keep surveillance for the introduction of new opportunistic pathogens into the population. ^

NMR structural analysis of cardiac troponin C: Monitoring conformational changes induced by binding calcium, troponin I, and calcium -sensitizing drugs

Contraction of cardiac muscle is regulated through the Ca2+ dependent protein-protein interactions of the troponin complex (Tn). The critical role cardiac troponin C (cTnC) plays as the Ca2+ receptor in this complex makes it an attractive target for positive inotropic compounds. In this study, the ten Met methyl groups in cTnC, [98% 13C ϵ]-Met cTnC, are used as structural markers to monitor conformational changes in cTnC and identify sites of interaction between cTnC and cardiac troponin I (cTnI) responsible for the Ca2+ dependent interactions. In addition the structural consequences that a number of Ca2+-sensitizing compounds have on free cTnC and the cTnC·cTnI complex were characterized. Using heteronuclear NMR experiments and monitoring chemical shift changes in the ten Met methyl 1H-13C correlations in 3Ca2+ cTnC when bound to cTnI revealed an anti-parallel arrangement for the two proteins such that the N-domain of cTnI interacts with the C-domain of cTnC. The large chemical shifts in Mets-81, -120, and -157 identified points of contact between the proteins that include the C-domain hydrophobic surface in cTnC and the A, B, and D helical interface located in the regulatory N-domain of cTnC. TnI association [cTnI(33–80), cTnI(86–211), or cTnI(33–211)] was found also to dramatically reduce flexibility in the D/E central linker of cTnC as monitored by line broadening in the Met 1H- 13C correlations of cTnC induced by a nitroxide spin label, MTSSL, covalently attached to cTnC at Cys 84. TnI association resulted in an extended cTnC that is unlike the compact structure observed for free cTnC. The Met 1H-13C correlations also allowed the binding characteristics of bepridil, TFP, levosimendan, and EMD 57033 to the apo, 2Ca2+, and Ca2+ saturated forms of cTnC to be determined. In addition, the location of drug binding on the 3Ca2+cTnC·cTnI complex was identified for bepridil and TFP. Use of a novel spin-labeled phenothiazine, and detection of isotope filtered NOEs, allowed identification of drug binding sites in the shallow hydrophobic cup in the C-terminal domain, and on two hydrophobic surfaces on N-regulatory domain in free 3Ca2+ cTnC. In contrast, only one N-domain drug binding site exists in 3Ca2+ cTnC·cTnI complex. The methyl groups of Met 45, 60 and 80, which are grouped in a hydrophobic patch near site II in cTnC, showed the greatest change upon titration with bepridil or TFP, suggesting that this is a critical site of drug binding in both free cTnC and when associated with cTnI. The strongest NOEs were seen for Met-60 and -80, which are located on helices C and D, respectively, of Ca2+ binding site II. These results support the conclusion that the small hydrophobic patch which includes Met-45, -60, and -80 constitutes a drug binding site, and that binding drugs to this site will lead to an increase in Ca2+ binding affinity of site II while preserving maximal cTnC activity. Thus, the subregion in cTnC makes a likely target against which to design new and selective Ca2+-sensitizing compounds. ^