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Visitors ( n = 2455) were surveyed at fourteen southern California beaches in the summer of 2009 to measure travel expenditures associated with a recreational beach trip. The majority of beach trips were made by California residents (88%), and most traveled by motorized vehicle (90%). Mean distance traveled per beach trip was 35.0 miles; mean time at the beach was 4.0 h; and mean age of adult visitors was 34.8 years. Amounts spent on different cost categories varied; Mean direct beach expenditures spent on parking, food, shopping, lodging and rentals were $46.09 per trip; mean fuel costs were $8.84 per trip; and mean equipment costs (beach gear) were $10.60 per trip. The combined Total Beach Expenditures (TBE) were $65.53 per trip. Beaches with amenities captured greater expenditures ($73.37 per trip) compared to beaches with less facilities ($11.78 per trip). Southern California beaches generate over $3.5 billion annually in beach related expenditures, and $2.5 billion of that is spent directly at beaches. Attendance patterns determine expenditure amounts resulting in more than half of direct beach expenditures occurring at only 20% of the regions most popular beach locations. The beach specific data and results on spending patterns can be helpful for a range of agencies and beach managers when researching the most economically effective maintenance or enhancement options for different sites. The values generated also provide baseline economic activity by beach which may be useful for compensation calculations in the event of a future loss or closure of a particular beach.

OBJECTIVES To examine the consequences of changing precipitation levels on southern California's recreational coastal water quality, and compare the responses of watersheds with differing levels of urban development. METHODS The geo-temporal relationship for six years (2000-2005) of precipitation levels, discharge rates for the ten primary waterways, and coastal water bacteria concentrations at seventy-eight southern California beaches were examined. RESULTS Precipitation levels, river-creek discharge rates, and coastal water bacteria concentrations were significantly correlated (p < 0.01) for all ten watersheds investigated. Water bacteria concentrations significantly increased with higher levels of precipitation across 95% of the seventy-eight beaches investigated. A heavily developed watershed had significantly higher median bacteria concentrations (186 cfu) in the adjoining coastal waters compared to an undeveloped watershed (10 cfu) of similar size. CONCLUSIONS Precipitation and ensuing runoff strongly control the rate of polluted water delivered to most beaches in southern California. Variable precipitation generates a greater response in coastal water bacteria concentrations in developed watersheds compared to undeveloped areas. Projected declines in regional precipitation as a consequence of climate change may result in less contaminated water delivered to coastal waters, thus decreasing risk of water associated illnesses during winter months.

Hematopoietic stem cells (HSCs) replicate (self-renew) to create 2 daughter cells with capabilities equivalent to their parent, as well as differentiate, and thus can both maintain and restore blood cell production. Cell labeling with division-sensitive markers and competitive transplantation studies have been used to estimate the replication rate of murine HSCs in vivo. However, these methods are not feasible in humans and surrogate assays are required. In this report, we analyze the changing ratio with age of maternal/paternal X-chromosome phenotypes in blood cells from females and infer that human HSCs replicate on average once every 40 weeks (range, 25-50 weeks). We then confirm this estimate with 2 independent approaches, use the estimate to simulate human hematopoiesis, and show that the simulations accurately reproduce marrow transplantation data. Our simulations also provide evidence that the number of human HSCs increases from birth until adolescence and then plateaus, and that the ratio of contributing to quiescent HSCs in humans significantly differs from mouse. In addition, they suggest that human marrow failure, such as the marrow failure that occurs after umbilical cord blood transplantation and with aplastic anemia, results from insufficient numbers of early progenitor cells, and not the absence of HSCs.

The longitudinal NHEXAS-Maryland study measured metals, PAHs, and pesticides in several media to capture temporal variability. Questionnaires were concurrently administered to identify factors that influenced changes in contaminant levels over time. We constructed mixed-effects regression models for lead, phenanthrene, and chlorpyrifos (including metabolites) in indoor air, dust, dermal wipes, and biological fluids. Significant predictors represented time-varying activities as well as unchanging housing and demographic factors. There was little overlap among the models, with predictors generally reflecting the diverse characteristics of the target compounds. We estimated between- and within-person variance components to evaluate the reliability of the measurements. While only one measurement of lead in blood or chlopyrifos in dust was needed for a dependable estimate of an individual's average level, three to eight measurements were needed for most other compound/exposure medium combinations because of considerable temporal variability. Measurements in biological fluids and dust were generally more consistent than those in indoor air. The significant covariates in the full models preferentially reduced the between-person variance component. Since the regression models explained only 1-37% of the within-person variance, the questionnaires in this study provided only modest insight into the factors responsible for the temporal variability in the contaminant levels.

Female Safari cats are offspring of domestic and Geoffroy parents, and are balanced heterozygotes with equal numbers of Blood cells containing domestic and Geoffroy-type glucose 6-phosphate dehydrogenase (G6PD),an X-chromosome derived enzyme. In previous studies, however, we observed increasing percentages of Blood cells with Geoffroy G6PD in cats aged 4–12 years. Similarly, ratios of parental X-chromosome phenotypes greater than three to one are common in women over age 60, while women under 40 typically exhibit one to one ratios. Using a two-compartment hidden-Markov model of the distribution of phenotype in samples taken during the second stage of hematopoiesis (Blood cell production), we estimate, through simulation and mathematical calculation, the Geoffroy selective advantages necessary to reproduce the data obtained from female Safari cats. It is shown that small differences in the kinetics of hematopoietic stem cells (HSC), less than might be detected by in vitro assays, can explain the “clonal dominance” observed with aging in cats, and by extension, human females. Conceptually, hematopoiesis in females can be viewed as a competitive exclusion process in which two populations of HSC (defined by parental X-chromosome phenotype) compete for environmental resources. As in many ecological examples, dominance may occur only after long periods of time.

The study examines the relationship between temporary welfare time limits and foster care relative placement in Nevada. A logit model was specified with a binary dependent variable capturing placement with relatives as opposed to nonrelative family foster care placement or group care. The findings reveal that, all else constant, children from welfare families with more months counted toward their Nevada's time limits are not more likely to be placed with relatives than their counterparts. The findings also show that children from African American families, from large families, or from families receiving cash during removal are more likely to be placed with relatives. The authors suggest that casework activities need to occur before, during, and after children experience foster care placements with relatives.

Objectives: (1) To quantify lethality of firearms relative to other suicide methods, (2) to quantify the extent to which suicide mortality may be reduced by limiting access to firearms. Methods: Data on suicides and hospitalised para-suicides that occurred in the state of Illinois from 1990 to 1997 were combined. Total number of episodes for each suicide method was estimated as the sum of the number of suicides and the number of para-suicides for that method. Gender and suicide method were used as proxies for intention to die, and estimated lethality of suicide methods within method-gender groups (for example, male firearm users). Logistic regression was used to quantify the lethality of firearms relative to other suicide methods. Excess mortality associated with the use of firearms was estimated by conservatively assuming that in the absence of firearms the next most lethal suicide method would be used. Results: From January 1990 to December 1997, among individuals 10 years or older in the state of Illinois, there were 37 352 hospital admissions for para-suicide and 10 287 completed suicides. Firearms are the most lethal suicide method. Episodes involving firearms are 2.6 times (95% CI 2.1 to 3.1) more lethal than those involving suffocation—the second most lethal suicide method. Preventing access to firearms can reduce the proportion of fatal firearms related suicides by 32% among minors, and 6.5% among adults. Conclusions: Limiting access to firearms is a potentially effective means of reducing suicide mortality.

This study analyzed interdependent behaviors among states in setting welfare benefits, behaviors often referred to as strategic interactions. Strategic interactions among states are believed to have led some state governments to "race to the bottom," o term used to describe state governments' decisions to cut welfare benefits when neighboring states have done the same. The study primarily examined the variations in strategic interactions by using spatial, temporal, and spatial-temporal statistical approaches. Findings suggest that both high and low benefit states pay attention to the generosity of their neighbors. Although more states have exerted pressure on benefit levels, this phenomenon has not abated over time nor has it intensified under welfare reform as anticipated by some economists. The present findings lead to the recommendation that a federal standard is warranted to eliminate some of the problems associated with decreasing benefits for families and children. Key words: block grants; "race to the bottom"; strategic interactions; welfare. benefit levels; welfare migration ********** The field of taxation often cites the view that a local government's policy choices in one locale are the results of the actions of other local governments. In the field of public welfare, views of interdependent behaviors among states, often referred to as strategic interactions, have become more common in recent years (Besley & Case, 1995; Case, Hines, & Rosen, 1993; Figlio, Koplin, & Reid, 1999). These behaviors are believed to have led some state governments to exert downward pressure on welfare benefits for needy families. The term "race" has been used widely to describe competition between states in setting welfare benefits. The term "race to the bottom" has been used to describe state governments' decisions to cut welfare benefits when their neighboring states have done the same (Figlio et al.). Some researchers maintain that under the current block grant structure, the race to the bottom has intensified because states bear the full cost of providing benefit payments to migrants from other states (Brueckner, 2000; Figlio et al., 1999). Along with time-limited welfare and stricter work and eligibility requirements, the enactment of the block grant structure occurred with the passage of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996 (P.L. 104193). This act eliminated the open-ended federal matching grant as a funding mechanism for the Aid to Families with Dependent Children (AFDC) program, now entitled Temporary Assistance for Needy Families (TANF), commonly known as welfare. Under the block grant system, each state receives a lump sum from the federal government. The size of the grant is independent of the state's contribution during a particular fiscal year. Strategic interactions among states are explanations for states' choices to decrease their benefits in absolute or real terms (Figilio et al., 1999; Saavedra, 1998). Earlier studies failed to examine closely how the race to the bottom varied across individual states. Most important, earlier studies did not examine whether the race had intensified since the implementation of the block grant structure. The present study provides an in-depth look at the extent to which strategic interaction varied across neighboring states and how this interaction changed over years. Spatial, temporal, and spatial-temporal approaches were used for analyses. The article discusses whether the race to the bottom has intensified in recent years under the block grant structure. We closely examined how and the extent to which states and their neighbors changed their welfare benefit levels relative to the national average benefit level. Last, by using a tree-based regression approach, we divided the country into regions where benefit levels are relatively homogeneous within each region yet quite different between the regions. …

OBJECTIVE: This study uses screening and hospitalization data to describe the prevalence of childhood lead poisoning in Chicago and the rest of the state of Illinois. METHODS: The authors used aggregate data published by the Illinois Department of Public Health on blood lead testing of children ages 0-6 years and data on lead-related hospital admissions of children ages 0-6 years, drawn from an administrative dataset compiled as part of a state initiative. RESULTS: No clear time trends in the percentage of children with elevated blood lead levels (defined as >15 micrograms per deciliter [microg/dL] or >45 microg/dL) were evident in either Chicago or the rest of Illinois. The proportions of children with elevated blood lead levels in Chicago and in the rest of Illinois did not decline at the dramatic rate seen in the US as a whole during the 1990s. Over a five-year period, in-hospital charges of $7.7 million were generated for the care of lead-poisoned children ages 6-16 in Chicago alone. CONCLUSION: Surveillance data, analyzed at the appropriate geographic level, can be used to focus resources on high-risk areas and to evaluate prevention efforts.

Hematopoiesis is the body's way of making the cellular constituents of blood. Oxygen transport, response to infections, and control of bleeding are among the functions of different mature blood cells. These specific functions are acquired as cells mature in the bone marrow. Stem cells are the “master cells” at the top of this pedigree, having within them the capacity to reconstitute the entire system. Although the latter stages of hematopoiesis are fairly well understood, the functioning of stem cells and other multipotential cells is currently a matter of intense research. This article presents a statistical analysis providing support for the clonal succession model of early hematopoiesis. J. L. Abkowitz and colleagues at the University of Washington have developed an experimental method for studying the kinetics of early hematopoiesis in a hybrid cat. The essence of the method is to analyze G6PD, an enzyme linked to the X chromosome. The G6PD type of a cell forms a binary marker that is passed ...

To study the behavior of hematopoietic stem cells in vivo, we transplanted glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats with small amounts of autologous marrow. The G6PD phenotypes of erythroid burst-forming units and granulocyte/macrophage colony-forming units were repeatedly assayed for 3.5-6 years after transplantation to track contributions of stem cell clones to the progenitor cell compartment. Two phases of stem cell kinetics were observed, which were similar to the pattern reported in comparable murine studies. Initially there were significant fluctuations in contributions of stem cell clones. Later clonal contributions to hematopoiesis stabilized. The initial phase of clonal disequilibrium, however, extended for 1-4.5 years (and not 2-6 months as seen in murine experiments). After this subsided, all progenitor cells from some animals expressed a single parental G6PD phenotype, suggesting that blood cell production could be stably maintained by the progeny of one (or a few) cells. As the hematopoietic demand of a cat (i.e., number of blood cells produced per lifetime) is over 600 times that of a mouse, this provides evidence that an individual hematopoietic stem cell has a vast self-renewal and/or proliferative capacity. The long phase of clonal instability may reflect the time required for stem cells to replicate sufficiently to reconstitute a large stem cell reserve.

Humans and larger mammals require more blood cells per lifetime than mice because of their larger size and longer life expectancy. To investigate this evolutionary adaptation, we calculated the total number of nucleated marrow cells (NMCs) per cat, observing the distribution of 59Fe to marrow, then multiplied this value (1.9 ± 0.9 × 1010 [mean ± SD]) times the frequency of feline hematopoietic stem cells (HSCs) (6 HSCs/107 NMCs) to derive the total number of HSCs per cat (11 400 ± 5400). Surprisingly, when the total number of HSCs per mouse was calculated with a similar experimental and computational approach, the value was equivalent. These data imply that the output of differentiated cells per feline HSC must vastly exceed that of murine HSCs. Furthermore, if the total number of human HSCs were also equivalent to the total number of HSCs in cat and mouse, the frequency of human HSCs would be 0.7 to 1.5 HSCs/108 NMCs, a frequency that is 20-fold less than estimated by the NOD/SCID repopulating assay.

To study clonal evolution in myeloproliferative disorders, we used stochastic models of hematopoiesis for mouse and cat, species for which the in vivo kinetics of hematopoietic stem cells (HSCs) have been experimentally defined. We determined the consequence if 1 HSC became able to survive without the support of a microenvironmental niche while the rest of its behavior did not change. Neoplastic cells persisted and dominated hematopoiesis in 14% of mice and 17% of cats, requiring mean times of 2.5 ± 0.5 and 7.0 ± 1.2 years, respectively (n = 1000 simulations/species). In both species, when the number of neoplastic HSCs exceeded 0.5% of all HSCs, clonal dominance was inevitable. Our results can explain the absence of clonal myeloproliferative disorders in mice (lifetime, 2 years), are consistent with clinical observations in cats, and provide insight into the progression of chronic myelogenous leukemia (CML) in humans. They also demonstrate that competition for microenvironmental support can lead to the suppression of normal hematopoiesis as neoplasia evolves. Toxic or immunologic suppression of normal HSCs is not required.

CARE-NMD is an EU-funded project to improve care for patients with Durchenne Muscular Dystrophy (DMD). The analysis of the current care practice is the first step to identify gaps and to plan specific measures such as training sessions for professionals and workshops for patients. For this purpose, a large cross-sectional patient-survey about the received care and quality of life of patients with DMD has been performed since September 2011 in seven European countries: Bulgaria, Czech Republic, Denmark, Germany, Hungary, Poland and the United Kingdom. A total of 1,677 patients with Duchenne Muscular Dystrophy have received questionnaires via the national patient registries. For the assessment of quality of care we defined outcome and process indicators. Outcome indicators include stage of the disease, age at loss of ambulation, ability to sit, number of hospitalisations, cardiac and pulmonary function and age at diagnosis. Process indicators comprise the frequency of medical assessments and received treatment, e.g. the use of corticosteroids, non-invasive ventilation and assistive devices. By March 31st 1,093 of 1,677 patients/families responded (66 percent). Response by country were: Bulgaria 45/73, Czech Republic 92/191, Denmark 92/131, Germany 440/545, Hungary 62/70, Poland 137/246, and for United Kingdom 223/421. Key findings about health status, received treatment, and quality of life of patients with DMD in Europe will be presented. This is the largest ever cross-sectional survey of the care and quality of life of people with DMD. The final results will provide detailed insight into the current situation of people with DMD in Europe and help to identify gaps to further improve the situation of affected patients and families.

Summary. We present a method for parameter estimation in a two-compartment hidden Markov model of the first two stages of hematopoiesis. Hematopoiesis is the specialization of stem cells into mature blood cells. As stem cells are not distinguishable in bone marrow, little is known about their behavior, although it is known that they have the ability to self-renew or to differentiate to more specialized (progenitor) cells. We observe progenitor cells in samples of bone marrow taken from hybrid cats whose cells contain a natural binary marker. With data consisting of the changing proportions of this binary marker over time from several cats, estimates for stem cell self-renewal and differentiation parameters are obtained using an estimating equations approach.

Inhaled concentration (C), minute volume (MV), and exposure duration (T) are factors that may affect the uptake of ozone (O3) within the respiratory tract. Ten healthy adult nonsmokers participated in four sessions, inhaling 0.2 or 0.4 ppm O3 through an oral mask while exercising continuously to elicit a MV of 20 l/min for 60 min or 40 l/min for 30 min. In each session, fractional absorption (FA) was determined on a breath-by-breath basis as the ratio of O3 uptake to the inhaled O3 dose. The mean ± SD value of FA for all breaths was 0.86 ± 0.06. Although C, MV, and T all had statistically significant effects on FA ( P < 0.0001, P = 0.004, and P = 0.026, respectively), the magnitudes of these effects were small compared with intersubject variability. For an average subject, a 0.05 change in FA would require that C change by 1.3 ppm, MV change by 46 l/min, or T change by 1.7 h. It is concluded that inhaled dose is a reasonable surrogate for the actual dose delivered to a particular subject during O3 exposures of

We simulated gene therapy using parameters derived from the analysis of autologous transplantation studies in glucose-6-phosphate dehydrogenase heterozygous cats to determine how hematopoietic stem cell (HSC) biology might influence outcomes. Simulation illustrates that a successful experiment can result by chance and may not be the repeated outcome of a specific protocol design or technical approach. As importantly, in many simulated gene therapy experiments where 1, 2, or 6 of 30 transplanted HSC were labeled, there was significant variation in the contribution from marked clones over time. Variability was minimized in simulations in which large numbers of HSC were transplanted. Strategies that may permit consistent clinically successful results are presented. Taken together, these simulation studies demonstrate that the in vivo behavior of HSC must be considered when optimizing approaches to gene therapy in large animals, and perhaps by extension, in humans.

To study the behavior of hematopoietic stem cells in vivo, hematopoiesis was simulated by assuming that all stem cell decisions (that is, replication, apoptosis, initiation of a differentiation/maturation program) were determined by chance. Predicted outcomes from simulated experiments were compared with data obtained in autologous marrow transplantation studies of glucose 6-phosphate dehydrogenase (G6PD) heterozygous female Safari cats. With this approach, we prove that stochastic differentiation can result in the wide spectrum of discrete outcomes observed in vivo, and that clonal dominance can occur by chance. As the analyses also suggest that the frequency of feline hematopoietic stem cells is only 6 per 10(7) nucleated marrow cells, and that sem cells do not replicate on average more frequently than once every three weeks, these large-animal data challenge clinical strategies for marrow transplantation and gene therapy.

Although the hematopoietic stem cell is an attractive target cell for gene transfer, little is known about its biology in vivo in large animals (or man). We have studied the in vivo behavior of hematopoietic stem cells in glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrasts the 2–6 months of clonal disequilibrium reported in comparable murine studies. Our data also suggests that hematopoietic stem cells do not self-renew more frequently than once per three weeks. These data may impact strategies for optimizing gene therapy in large animals, and by extension in man.

CARE-NMD aims to disseminate and implement best-practice standards of care for Duchenne muscular dystrophy (DMD) in Europe. Patient registries offer a valuable approach to engaging with the patient community, both to disseminate information and to survey their experiences. Registries permit the identification of a patient population with a precise genetic diagnosis, and are thus essential to the development of novel, mutation-specific therapeutic approaches such as exon-skipping. A core driving factor in their development has often therefore been clinical trial readiness: e.g. determining trial viability for a specific genetic mutation. However, as registries enable contact with a patient population, they also offer research opportunities outside the clinical trial domain. These include surveying availability of high-quality care and quality of life issues. Furthermore, registries permit the distribution of care information aimed at that particular audience. CARE-NMD has utilised patient registries in both of these contexts. The project has promoted knowledge of best-practice care via the translation and dissemination of the Family Guide to the care standards. This is now available in 22 languages via the CARE-NMD and TREAT-NMD websites, with 200 monthly downloads. The project has also conducted, via national patient registries in seven countries (Bulgaria, Czech Republic, Denmark, Germany, Hungary, Poland, and the UK), the largest ever survey of care and quality of life for DMD. The overall response rate is 66%, with 1100 responses received (April 2012), and national response rates of 48–89%. The data gathered provide unparalleled information on the experience of patients and families living with DMD across Europe. The use of registries also enables the return of information to the patient community, enhancing patient-led advocacy for the availability of better care, and strengthening mutual understanding between rare disease researchers and the patient community.

CARE-NMD aims to disseminate and implement best-practice standards of care for Duchenne muscular dystrophy (DMD) in Europe. As part of the project a survey of health related quality of life was to be conducted in seven countries. To select relevant methods of measurement a screening of seven existing instruments was carried out. Main criteria for selection were frequency of use, correspondence with domains in the International Classification of Functioning, Disability and Health (ICF), comparability with background population, and scope of cross cultural and geographical assessments. Three pediatric (one disease specific and two generic) and two (generic) instruments were chosen. A comprehensive questionnaire containing the selected instruments was designed and implemented through patient registries in Bulgaria, Czech Republic, Denmark, Germany, Hungary, Poland, and the UK. The overall response rate was 66%. In addition to information on the experience of 1100 European patients and families living with DMD, the data will provide important knowledge about the options and feasibilities of cross national QoL assessments in Duchenne muscular dystrophy.

Abstract 2522 Poster Board II-499 The replication kinetics of HSC in vivo is difficult to assess because HSC are infrequent, reside in marrow niches, and are regulated by extrinsic as well as intrinsic signals. Determining the replication (self-renewal) rate of human HSC in vivo is especially difficult because limiting dilution competitive transplantation studies and studies with cell division-sensitive markers are not feasible. Therefore, we developed three surrogate methods by extending observations in other species. These approaches use different data and different assumptions yet yield overlapping estimates and together suggest that human HSC replicate on average once per 40 weeks. This is thus much slower than replication rates of HSC in mouse (∼ once per 2.5 wks), cat (∼ once per 8.3 -10 wks) and nonhuman primate (∼ once per 25 wks) (reviewed in 1). Specifically, we analyzed the drift in the X-chromosome phenotype of blood cells from 1219 females (ages 18 -100, mean 56±22; Montreal cohort) assuming that HSC expressing X-alleles from one parent might divide slightly faster than HSC expressing X-alleles from the other parent and that over time this subtle growth advantage would lead to the phenotypic skewing of HSC and progeny cells. We calculated that the drift that occurs with aging in the X-chromosome phenotype of granulocytes in female Safari cats (F1 offspring of Geoffroyi (G) x domestic (d) cats) can be explained by a 5% difference in the replication rates of HSC expressing G vs. d X-chromosomes. Knowing that G and d cats evolved independently for > 9 million yrs, we simulated human hematopoiesis using a Markovian description of HSC differentiation and the single constraint that the differences in the replication rates of HSC expressing paternal vs. maternal-derived X-chromosomes in individual human females (150,000 yrs of genetic distance) would be less than 5%. For each replication rate (λ), we generated 100 sets of 1219 virtual females (the replication rates of HSC expressing maternal and paternal X-chromosomes in each individual were randomly drawn from a distribution with median λ and variance as observed in Safari cats) and determined if the pattern of X-chromosome phenotype in their blood cells with aging resembled the Montreal data. If yes, λ was included as a possible human HSC replication rate and if no, it was excluded. Using this approach, we defined plausible values for λ, then confirmed the results by a comparable analysis of second dataset (London cohort; 117 females, ages 18–96, mean 66±24). Remarkably, this value (1 per 40 wks; range 1 per 25–50 wks) is also consistent with estimates derived by two independent methods: analysis of granulocyte telomere length with aging2 and application of the concept that the total number of HSC divisions during a mammal's lifetime is evolutionarily conserved (data not shown). We next demonstrated that the estimate was reasonable by simulating human marrow transplantation. When 100 HSC are transplanted (corresponds to 1.9 ×108 marrow cells (MC)/kg, 70 kg recipient), all virtual recipients engraft, consistent with the clinical recommendation that >2–3 × 108 MC/kg be transplanted. Also, when 20 HSC are transplanted (3.9 ×107 MC/kg), graft failure is common (occurs in 50% of simulations). Of interest, these virtual recipients run out of short-term repopulating cells (STRC) within 30 wks, though HSC persist. There are several clinically relevant corollaries to this latter observation. First, children (small size, fewer mature blood cells) tolerate transplantations of fewer HSCs better than adults because few STRC can produce safe numbers of granulocytes, red cells and platelets. Second, supplementing transplantations with infusions of multipotent progenitor cells, such as present in cytokine or Notch ligand Delta1-expanded cord blood, should be an efficacious method to insure adequate hematopoiesis when the numbers of HSC are low and STRC are especially low. The data also raise the possibility that human marrow failure syndromes such as aplastic anemia and myelodysplasia could result from defective HSC commitment or defective expansion of differentiating STRC clones, and not only from the destruction or depletion of HSC. These events may be difficult to study in mice where simulations predict graft failure occurs from HSC depletion (data not shown), justifying the need for larger animal (cat, dog, primate) or human investigation. 1 Blood 110:1806,2007. 2Exp Hematol 32:1014,2004. Disclosures: No relevant conflicts of interest to declare.

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