Schizencephaly in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs. MATERIALS AND METHODS: A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities. RESULTS: Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs. CONCLUSIONS: To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.

Childhood obesity, weight loss and developmental trajectories predict the persistence and remission of childhood sleep-disordered breathing.

BACKGROUND: Obesity has been recognized as a risk factor for childhood sleep-disordered breathing (SDB), yet it remains unclear how obesity and weight change predict the course of childhood SDB. OBJECTIVE: The objective of the study is to investigate the role of body weight, upper airway abnormalities and developmental trajectories on the persistence and remission of childhood SDB in the transition to adolescence. METHODS: The Penn State Child Cohort is a representative population sample of 700 children (5-12 years), of whom 421 were followed up as adolescents (12-23 years). Participants underwent a clinical history, physical examination and polysomnography at both time points. RESULTS: Obesity and enlarged tonsils were cross-sectionally associated with childhood SDB. Longitudinally, baseline obesity predicted the persistence of childhood SDB (OR = 3.75, 95% CI = 2.00-7.05), while weight loss predicted its remission (OR = 1.67, 95% CI = 1.11-2.50). Children with enlarged tonsils who remitted from SDB had not experienced significant weight loss and only 4.4% had undergone adeno/tonsillectomy. Body fat distribution/composition at follow-up was similar in those who had remitted from childhood SDB as compared with those who had never experienced SDB, while those who persisted with childhood SDB showed significant android distribution and visceral adiposity at follow-up. CONCLUSIONS: Our data support a causal role for obesity and weight loss in the chronicity and remission, respectively, of childhood SDB in the transition to adolescence and suggest that remission of SDB is related to developmental trajectories of the upper airway in a significant proportion of children. Thus, targeting childhood obesity and weight gain should be a priority in the prevention and treatment of SDB during this critical developmental period.

Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins.

Neurocognitive and behavioral functioning in adolescents with sleep-disordered breathing: a population-based, dual-energy X-ray absorptiometry study.

BACKGROUND/OBJECTIVES: Sleep-disordered breathing (SDB) has been associated with neurocognitive and behavioral problems in young children; however, this association is less studied in adolescents. Evidence suggests that obesity plays a key role in the development of SDB, although its relative association with neurobehavioral functioning remains unclear. We examined whether SDB and obesity are associated with neurocognitive and behavioral problems in adolescents. SUBJECTS/METHODS: A total of 421 adolescents (17.0±2.2y, 53.9% male) from the Penn State Child Cohort, a general population sample, underwent a 9-h polysomnography, clinical history, physical examination, neurocognitive evaluation and Dual-energy X-ray Absorptiometry (DXA) scan, and completed the Child or Adult Behavior Checklist. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI)⩾2, primary snoring (PS) as AHI<2+snoring and no-SDB as AHI<2 without snoring. Body weight measures included body mass index (BMI) percentile, waist circumference (WC) and DXA-measured total adipose tissue (TAT). RESULTS: WC and TAT were significantly associated with impaired vigilance, processing speed, working memory, and control interference and greater internalizing and externalizing behaviors, while BMI percentile was marginally associated. SDB per se (PS, AHI or OSA) was not significantly associated with impaired neurocognitive outcomes or greater behavioral problems. However, TAT was significantly associated with impaired vigilance and greater internalizing and externalizing behaviors and, to a lesser extent, slower processing speed and greater control interference, only in adolescents with OSA. CONCLUSIONS: Central obesity, an etiopathogenic mechanism of OSA, is more strongly associated with neurocognitive and behavioral problems in adolescents than SDB alone. Deficits in low-order (vigilance) and high-order (executive) functions and behavioral problems observed in adolescents with OSA are primarily associated with increased central adiposity, a finding not entirely captured with less precise measures of obesity. These data support that OSA and its associated neurocognitive and behavioral morbidity are related to underlying metabolic dysfunction as early as adolescence.

Addressing location uncertainties in GPS-based activity monitoring: A methodological framework.

Location uncertainty has been a major barrier in information mining from location data. Although the development of electronic and telecommunication equipment has led to an increased amount and refined resolution of data about individuals' spatio-temporal trajectories, the potential of such data, especially in the context of environmental health studies, has not been fully realized due to the lack of methodology that addresses location uncertainties. This article describes a methodological framework for deriving information about people's continuous activities from individual-collected Global Positioning System (GPS) data, which is vital for a variety of environmental health studies. This framework is composed of two major methods that address critical issues at different stages of GPS data processing: (1) a fuzzy classification method for distinguishing activity patterns; and (2) a scale-adaptive method for refining activity locations and outdoor/indoor environments. Evaluation of this framework based on smartphone-collected GPS data indicates that it is robust to location errors and is able to generate useful information about individuals' life trajectories.

Packing in protein cores.

Proteins are biological polymers that underlie all cellular functions. The first high-resolution protein structures were determined by x-ray crystallography in the 1960s. Since then, there has been continued interest in understanding and predicting protein structure and stability. It is well-established that a large contribution to protein stability originates from the sequestration from solvent of hydrophobic residues in the protein core. How are such hydrophobic residues arranged in the core; how can one best model the packing of these residues, and are residues loosely packed with multiple allowed side chain conformations or densely packed with a single allowed side chain conformation? Here we show that to properly model the packing of residues in protein cores it is essential that amino acids are represented by appropriately calibrated atom sizes, and that hydrogen atoms are explicitly included. We show that protein cores possess a packing fraction of [Formula: see text], which is significantly less than the typically quoted value of 0.74 obtained using the extended atom representation. We also compare the results for the packing of amino acids in protein cores to results obtained for jammed packings from discrete element simulations of spheres, elongated particles, and composite particles with bumpy surfaces. We show that amino acids in protein cores pack as densely as disordered jammed packings of particles with similar values for the aspect ratio and bumpiness as found for amino acids. Knowing the structural properties of protein cores is of both fundamental and practical importance. Practically, it enables the assessment of changes in the structure and stability of proteins arising from amino acid mutations (such as those identified as a result of the massive human genome sequencing efforts) and the design of new folded, stable proteins and protein-protein interactions with tunable specificity and affinity.

Collective repacking reveals that the structures of protein cores are uniquely specified by steric repulsive interactions.

Protein core repacking is a standard test of protein modeling software. A recent study of six different modeling software packages showed that they are more successful at predicting side chain conformations of core compared to surface residues. All the modeling software tested have multicomponent energy functions, typically including contributions from solvation, electrostatics, hydrogen bonding and Lennard-Jones interactions in addition to statistical terms based on observed protein structures. We investigated to what extent a simplified energy function that includes only stereochemical constraints and repulsive hard-sphere interactions can correctly repack protein cores. For single residue and collective repacking, the hard-sphere model accurately recapitulates the observed side chain conformations for Ile, Leu, Phe, Thr, Trp, Tyr and Val. This result shows that there are no alternative, sterically allowed side chain conformations of core residues. Analysis of the same set of protein cores using the Rosetta software suite revealed that the hard-sphere model and Rosetta perform equally well on Ile, Leu, Phe, Thr and Val; the hard-sphere model performs better on Trp and Tyr and Rosetta performs better on Ser. We conclude that the high prediction accuracy in protein cores obtained by protein modeling software and our simplified hard-sphere approach reflects the high density of protein cores and dominance of steric repulsion.

Spatially Analyzing the Inequity of the Hong Kong Urban Heat Island by Socio-Demographic Characteristics.

Recent studies have suggested that some disadvantaged socio-demographic groups face serious environmental-related inequities in Hong Kong due to the rising ambient urban temperatures. Identifying heat-vulnerable groups and locating areas of Surface Urban Heat Island (SUHI) inequities is thus important for prioritizing interventions to mitigate death/illness rates from heat. This study addresses this problem by integrating methods of remote sensing retrieval, logistic regression modelling, and spatial autocorrelation. In this process, the SUHI effect was first estimated from the Land Surface Temperature (LST) derived from a Landsat image. With the scale assimilated to the SUHI and socio-demographic data, a logistic regression model was consequently adopted to ascertain their relationships based on Hong Kong Tertiary Planning Units (TPUs). Lastly, inequity "hotspots" were derived using spatial autocorrelation methods. Results show that disadvantaged socio-demographic groups were significantly more prone to be exposed to an intense SUHI effect: over half of 287 TPUs characterized by age groups of 60+ years, secondary and matriculation education attainment, widowed, divorced and separated, low and middle incomes, and certain occupation groups of workers, have significant Odds Ratios (ORs) larger than 1.2. It can be concluded that a clustering analysis stratified by age, income, educational attainment, marital status, and occupation is an effective way to detect the inequity hotspots of SUHI exposure. Additionally, inequities explored using income, marital status and occupation factors were more significant than the age and educational attainment in these areas. The derived maps and model can be further analyzed in urban/city planning, in order to mitigate the physical and social causes of the SUHI effect.

Spatial cluster detection of air pollution exposure inequities across the United States.

Air quality is known to be a key factor in affecting the wellbeing and quality of life of the general populous and there is a large body of knowledge indicating that certain underrepresented groups may be overexposed to air pollution. Therefore, a more precise understanding of air pollution exposure as a driving cause of health disparities between and among ethnic and racial groups is necessary. Utilizing 52,613 urban census tracts across the United States, this study investigates age, racial, educational attainment and income differences in exposure to benzene pollution in 1999 as a case. The study examines spatial clustering patterns of these inequities using logistic regression modeling and spatial autocorrelation methods such as the Global Moran's I index and the Anselin Local Moran's I index. Results show that the age groups of 0 to 14 and those over 60 years old, individuals with less than 12 years of education, racial minorities including Blacks, American Indians, Asians, some other races, and those with low income were exposed to higher levels of benzene pollution in some census tracts. Clustering analyses stratified by age, education, and race revealed a clear case of disparities in spatial distribution of exposure to benzene pollution across the entire United States. For example, people aged less than 4 years from the western south and the Pacific coastal areas exhibit statistically significant clusters. The findings confirmed that there are geographical-location based disproportionate pattern of exposures to benzene air pollution by various socio-demographic factors across the United States and this type of disproportionate exposure pattern can be effectively detected by a spatial autocorrelation based cluster analysis method. It is suggested that there is a clear and present need for programs and services that will reduce inequities and ultimately improve environmental conditions for all underrepresented groups in the United States.

The effect of a low and high resource intervention on older drivers' knowledge, behaviors and risky driving.

This study aimed to compare an in-class Seniors on the MOVE (Mature Operators Vehicular Education) interactive multi-session driving curriculum with a self-guided MOVE curriculum for older adults. Using a two group randomized design, we sought to determine if there are between-group differences in older drivers' knowledge and safety behaviors among participants. Forty-four participants with an average age of 79 years (SD=7.1) were randomly assigned to the original MOVE program (SOM-A) or a lower resource (SOM-B) self-guided intervention. SOM-A is a four session program designed to improve older drivers safety knowledge and better understand skills for safer driving. SOM-B is a self-guided program with one required in-class session and one optional session. Subsequent to completion of both curricula, participants were offered CarFit, a comprehensive check of how well a senior driver and their vehicle work together. Baseline, post-intervention and 6-month follow up questionnaires were completed by participants. We found significant differences (p=.01) in the mean driving safety knowledge scores when comparing participants in SOM-A (3.7, SD 2.0) to those in SOM-B (0.87, SD 2.6). With regard to behavioral outcomes, we focused on always wearing a seatbelt, talking with a health care provider about driving ability, and sitting 10-12 inches from the steering wheel. The vast majority of participants reported always wearing their seat belts (SOM-A 100%, SOM-B 92%, p=1.0), and very few reported talking with their doctors (SOM-A Baseline--0%, Follow up 1--0%, p=n/a). Mean behavior change scores for participants sitting 10-12 inches from the steering wheel were significantly more likely among SOM-A (mean=.65, SD=.5) participants than those in SOM-B (mean=.29, SD=.5, p=.01) at first follow-up. Taken together, these findings suggest that the more intensive program is more effective and that driving safety programs focused on behaviors to self evaluate driving abilities continue to be needed to help older drivers remain safer on the road as they age. The involvement of health care providers in such efforts may be an untapped potential.

Product formulation for ohmic heating: blanching as a pretreatment method to improve uniformity in heating of solid-liquid food mixtures.

The electrical conductivity of food components is critical to ohmic heating. Food components of different electrical conductivities heat at different rates. While equal electrical conductivities of all phases are desirable, real food products may behave differently. In the present study involving chicken chow mein consisting of a sauce and different solid components, celery, water chestnuts, mushrooms, bean sprouts, and chicken, it was observed that the sauce was more conductive than all solid components over the measured temperature range. To improve heating uniformity, a blanching method was developed to increase the ionic content of the solid components. By blanching different solid components in a highly conductive sauce at 100 degrees C for different lengths of time, it was possible to adjust their conductivity to that of the sauce. Chicken chow mein samples containing blanched particulates were compared with untreated samples with respect to ohmic heating uniformity at 60 Hz up to 140 degrees C. All components of the treated product containing blanched solids heated more uniformly than untreated product. In sensory tests, 3 different formulations of the blanched product showed good quality attributes and overall acceptability, demonstrating the practical feasibility of the blanching protocol.

Difference between blocking and Néel temperatures in the exchange biased Fe3O4/CoO system.

The blocking temperature T(B) has been determined as a function of the antiferromagnetic layer thickness in the Fe3O4/CoO exchange biased system. For CoO layers thinner than 50 A, T(B) is reduced below the Néel temperature T(N) of bulk CoO (291 K), independent of crystallographic orientation or film substrate ( alpha-Al2O3, SrTiO3, and MgO). Neutron diffraction studies show that T(B) does not track the CoO ordering temperature and, hence, that this reduction in T(B) does not arise from finite-size scaling. Instead, the ordering temperature of the CoO layers is enhanced above the bulk T(N) for layer thicknesses approximately less than or equal to 100 A due to the proximity of magnetic Fe3O4 layers.

Menstrual patterns and fecundity among non-lactating and lactating cycling women in rural highland Bolivia: implications for contraceptive choice.

Choosing an appropriate contraceptive method, particularly one based on fertility awareness, depends in part upon the degree of a woman's cycling regularity. However, while the suppressive effect of lactation on ovarian function is well established, the potential influence of continued breastfeeding on menstrual patterns once post-partum cycling has resumed is largely unexamined. This longitudinal study in a population of non-contracepting Aymara women (n = 191 providing 665 non-truncated menstrual segments) identified conceptions and fetal loss via urine tests for hCG and classified segments accordingly to test the hypotheses that (1) cycles in lactating women are significantly different in length and regularity from those of non-lactating women, and (2) cycles in women living at high altitude are significantly different in length and regularity from those at lower altitudes. Analyses found that segments are significantly longer and regularity tends to be less common among lactating than non-lactating women; however, the rate of conception is twice as great among the former than the latter, and the distribution of conception outcomes does not differ between the two groups. Menstrual regularity is not the norm in this population, even among those who are not currently breastfeeding. High altitude per se does not appear to influence menstrual cycling as both regularity and segment length are comparable to other populations, hence women indigenous to high altitude are suitable candidates for a wide variety of contraceptive choices. In addition, these findings suggest that studies of fecundability limited to non-lactating women may be biased towards those of relatively lower fecundity.

Isokinetic strength testing in research and practice.

Age-related losses in lower extremity strength result in functional disabilities that diminish the quality of life for many older adults. Multiple factors, including type of muscle fiber, size of the muscle, length and speed of the muscle at contraction, age, and gender, affect the magnitude of strength generated. Assessment in clinical practice, in order to be cost and time effective, screens older adults for loss in strength. Further evaluation of strength loss requires the use of sophisticated procedures and equipment. Research into the causes of loss of strength and interventions to lessen or prevent loss of strength requires valid and reliable assessment tools. This article examines components of isokinetic muscle strength, the measurement of strength in clinical practice, methods to measure isokinetic strength, and validity and reliability of these measures.

Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis.

Quantitative relations between dietary fat and cholesterol and plasma lipid concentrations have been the subject of much study and some controversy during the past 40 y. Previous meta-analyses have focused on the most tightly controlled, highest-quality experiments. To test whether the findings of these investigations are generalizable to broader experimental settings and to the design of practical dietary education interventions, data from 224 published studies on 8143 subjects in 366 independent groups including 878 diet-blood lipid comparisons were subjected to weighted multiple-regression analysis. Inclusion criteria specified intervention studies published in English between 1966 and 1994 reporting quantitative data on changes in dietary cholesterol and fat and corresponding changes in serum cholesterol, triacylglycerol, and lipoprotein cholesterol concentrations. Regression models are reported for serum total cholesterol, triacylglycerol, and low-density-high-density-, and very-low-density-lipoprotein cholesterol, with multiple correlations of 0.74, 0.65, 0.41, 0.14, and 0.34, respectively. Interactions of dietary factors, initial dietary intakes and serum concentrations, and study and subject characteristics had little effect on these models. Predictions indicated that compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg cholesterol/d) will reduce plasma total and low-density-lipoprotein-cholesterol concentrations by approximately 5% compared with amounts associated with the average American diet.

Efficient segmentation of large-area skin images: a statistical evaluation.

BACKGROUND/AIMS: This paper is the second of a series describing research and development performed by the SPOTS project towards automating the process of monitoring pigmented lesions for change over time. Several parameters of the system are introduced along with the methods used for determining appropriate settings. We then describe our experimental setup and present a detailed statistical analysis to evaluate system performance. METHODS: There exist three sets of parameters in our system related to image segmentation, classification, and a region-growing step that can be individually tuned. The multiresolution hierarchical segmentation algorithm contains both a set of weights for the tristimulus color values used in calculating color differences and a contrast threshold used to identify root nodes that represent image segments. These were tuned using a synthetic image to simulate a pigmented lesion with irregular border and by estimating the parameters by successive approximations. The neural network classification used to detect lesion segments was trained using a 10-fold cross-validation, and the output classification threshold was set to yield a small false negatives ratio. Finally, there is a growing threshold used to determine whether neighbor regions should be merged in the region-growing step that was selected to minimize the change in area for different translations of a synthetic lesion. In order to evaluate the performance of the system, we compared the identified lesions with manually localized lesions. Ten images of the same area were taken from two subjects presenting lesions of varying size and different background skin texture. A sample of two images from the set was used to simulate variations in acquisition. Five operators were asked to trace lesion boundaries in two passes, separated by a few days, to evaluate the consistency of operators among themselves. The system was then run on the images using the optimal set of parameters. The results were analyzed for independent observation, matched pass, and doubly-matched pass data. CONCLUSIONS: Independent observation data indicates that the system finds significantly more objects than any of the human operators, but the areas reported are not significantly different on average. Matched pass data show that the correlations of the system with human operators is quite high. The system agrees with humans only slightly less than they do among themselves and has a tendency to report slightly smaller areas. The correlation between system and human peformance was further reinforced by the doubly-matched arrangement. These results indicate that our system is as reliable and consistent as our human reference, yielding similar performance.

Order writing for parenteral nutrition by registered dietitians.

OBJECTIVES: The purpose of the study was to describe the involvement of registered dietitians in parenteral nutrition (PN) orders, to identify characteristics of those who write orders; and to rank education, training, and support elements that dietitians believe facilitate PN order-writing skills. DESIGN: Mail survey method. SUBJECTS: Usable returned questionnaires (n = 266) represented randomly sampled membership of the Dietitians in Nutrition Support (a dietetic practice group of The American Dietetic Association) and registered dietitian membership of the American Society of Parenteral and Enteral Nutrition. STATISTICAL ANALYSIS: Data were analyzed using basic frequency displays on all questionnaire items, Pearson correlations between the quantitative variables, and one-way analysis of variance with each of the categorical variables and the quantitative variables. Detail exploration among variables was done by chi(2) analyses and two-tailed t tests. RESULTS: "Recommend" was the most frequent response to a query about participation in PN orders. An average of 37% of respondents sometimes or always wrote orders for nutrients. Specialists were more likely to write orders than clinicians and managers. No relationship was found between those who wrote orders and educational level, and writers had been registered for a shorter length of time. Agreement on the training and support needed for order-writing skills was nearly unanimous. APPLICATIONS: The PN skills of respondents who were specialists distinguished them from managers and clinicians. Specialists did not fit criteria for advanced practice, and specialty practice in metabolic nutrition care may be too broad to define their practice. Educators must recognize the importance of including PN training in didactic and clinical training programs. Registered dietitians with PN skills will be well positioned to play an active role in the evolving health care system.

Influence of a statewide trauma system on location of hospitalization and outcome of injured patients.

OBJECTIVE: Evaluate the influence of implementing the Oregon statewide trauma system on admission distribution and risk of death. DESIGN: Retrospective pre- and posttrauma system analyses of hospital discharge data regarding injured patients with one or more of the following injuries: head, chest, spleen/liver, pelvic fracture, and femur/tibia fracture. MATERIALS AND METHODS: Risk-adjusted odds ratio of admission to Level I or II (tertiary care) trauma centers, and odds ratio of death were determined using hospital discharge abstract data on 27,633 patients. Patients treated in 1985-1987, before trauma system establishment, were compared to patients treated in 1991-1993 after the trauma system was functioning. MEASUREMENTS AND MAIN RESULTS: After trauma system implementation, the odds ratio of admission to Level I or II trauma centers increased (odds ratio 2.36, 95% confidence interval 2.24-2.49). In addition, the odds ratio of death for injured patients declined after trauma system establishment (odds ratio 0.82, confidence interval 0.73-0.92). CONCLUSIONS: The Oregon trauma system was successfully implemented with more patients with index injuries admitted to hospitals judged most capable of managing trauma patients. The Oregon trauma system also appears beneficial since trauma system establishment is associated with a statewide reduction in risk of death.