Survival ability of Mexican fruit fly males from different strains in presence of the predatory orb-weaving spider Argiope argentata (Araneae: Araneidae).

The sterile insect technique (SIT) is a key element for the integrated management of pest populations of the Mexican fruit fly, Anastrepha ludens, in Mexico. Its success depends on the survival of mass-reared sterile males and their ability to mate with wild females. However, colonization and mass-rearing conditions can adversely affect their ability to avoid predators. To test if colony management strategies could contribute to improve field survival abilities of mass-reared flies, we compared the survival of males exposed to the orb-weaver spider Argiope argentata. Males compared originated from three strains with different colonization strategies: (a) a colony started from field-collected wild flies (replacement), (b) a colony started by hybridizing wild males with mass-reared adapted females (hybrid) and (c) a colony started with mass-reared males selected on the basis of their survival ability and mating competitiveness in field cages (selected). Mass-reared males and wild males were used as controls. Males were exposed to spiders under laboratory cage conditions. Overall, wild males showed better survival ability than mass-reared males. Regarding the colonization approach, wild males survived better than a hybrid, replaced and selected males. We conclude that mass-rearing conditions have a strong negative effect on the ability of males to escape spiders. The colonization systems evaluated did not counter this effect. The lower survival of males from the selected colony suggests that the selection over one generation did not contribute to improve males' predator avoidance and escape abilities and probably needs to be modified. Possible explanations for this and implications on colonization and colony management for SIT purpose are discussed.

Efficiency of two larval diets for mass-rearing of the mosquito Aedes aegypti.

Aedes aegypti is a major vector of arboviruses that may be controlled on an area-wide basis using the sterile insect technique (SIT). Larval diet is a major factor in mass-rearing for SIT programs. We compared dietary effects on immature development and adult fitness-related characteristics for an International Atomic Energy Agency (IAEA) diet, developed for rearing Ae. albopictus, and a standardized laboratory rodent diet (LRD), under a 14:10 h (light:dark) photoperiod ("light" treatment) or continuous darkness during larval rearing. Larval development was generally fastest in the IAEA diet, likely reflecting the high protein and lipid content of this diet. The proportion of larvae that survived to pupation or to adult emergence did not differ significantly between diets or light treatments. Insects from the LRD-dark treatment produced the highest proportion of male pupae (93% at 24 h after the beginning of pupation) whereas adult sex ratio from the IAEA diet tended to be more male-biased than that of the LRD diet. Adult longevity did not differ significantly with larval diet or light conditions, irrespective of sex. In other aspects the LRD diet generally performed best. Adult males from the LRD diet were significantly larger than those from the IAEA diet, irrespective of light treatment. Females from the LRD diet had ~25% higher fecundity and ~8% higher egg fertility compared to those from the IAEA diet. Adult flight ability did not differ between larval diets, and males had a similar number of copulations with wild females, irrespective of larval diet. The LRD diet had lower protein and fat content but a higher carbohydrate and energetic content than the IAEA diet. We conclude that the LRD diet is a low-cost standardized diet that is likely to be suitable for mass-rearing of Ae. aegypti for area-wide SIT-based vector control.

The relationship between alternative medication possession ratio thresholds and outcomes: evidence from the use of glatiramer acetate.

OBJECTIVE: To examine how changes in the medication possession ratio (MPR) affect the probability of multiple sclerosis (MS) relapses and total and MS-related charges among patients treated with glatiramer acetate (GA). METHODS: Data were obtained from i3 InVision™ Data Mart for January 1, 2006 through March 31, 2010. Patients were included if they were diagnosed with MS, initiated therapy with GA, and had continuous insurance coverage from 6 months prior through 24 months after initial use of GA (n=839). Multivariate regressions which controlled for patient characteristics examined the association between achievement of alternative MPR goals and patient relapses and charges. RESULTS: Patients who achieved an MPR of at least 0.7 had significantly lower odds of relapse than those with MPR thresholds below 0.7, with achievement of a threshold of 0.7, 0.8, or 0.9, associated with an odds ratio of relapse of 0.545 (95% CI=0.351-0.824), 0.568 (95% CI=0.371-0.870), and 0.421 (95% CI=0.260-0.679), respectively. Attaining higher MPR thresholds resulted in larger reductions in direct medical charges, excluding GA and other MS-related drugs. MPR of 0.25 was associated with $1699 lower 2-year total direct medical charges (p=0.009) while a threshold of 0.95 was associated with $2136 lower total charges (p<0.001), compared to patients not reaching these respective thresholds. MPR of 0.90 was associated with $986 lower MS-related charges than for those with MPR<0.90 (p=0.050). Results also revealed an association between patient adherence to GA and statistically significant reductions in charges for specific components of care. LIMITATIONS: Results are generalizable only to patients with medical and prescription benefit coverage without regard for functional status. CONCLUSIONS: As adherence improved the odds of relapse decreased and charge offsets generally increased. Results suggest that, despite higher costs associated with increased usage of GA, patient outcomes are improved and there are cost-offsets associated with adherent use of GA.

Production of leukotriene C4 by peripheral blood leukocytes stimulated with anti-fcepsilonRI antibody, PMA, and fMLP does not correlate with irreversible airway obstruction in asthmatics.

BACKGROUND: Airway remodeling has recently emerged as a major problem in an increasing percentage of patients with asthma. Reasons for great diversity in the progression of irreversible bronchoconstriction among asthmatics remain unclear. OBJECTIVE: The aim of this study was to assess whether the potential ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli is correlated with magnitude of irreversible airway obstruction in asthmatics. MATERIALS AND METHODS: The study sample comprised 76 asthmatics (34 males, mean +/- SD age 52 +/- 13 years), and 35 healthy controls (18 males, 38.2 +/- 15 years). Each subject underwent 2 pulmonary function tests: before and after bronchodilator administration. In addition, approximate annual decline in forced expiratory volume in 1 second (FEV1) (% of predicted) was calculated. Leukotriene C4 (LTC4) production was assessed combining a cellular antigen stimulation test and enzyme-linked immunosorbent assay using Bulhmann Laboratories AG kits. Leukocytes isolated from peripheral blood were stimulated with anti-FcepsilonRI antibody, N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). In separate tubes each subject's leukocytes were tested for spontaneous LTC4 production. Finally, stimulated LTC4 production was expressed in pg/mL after subtraction of values of spontaneous production. RESULTS: In asthmatics, baseline FVC% and FEV% values ranged from 24.4% to 122.4% (mean, 75.5%) and from 23.4% to 126.6% (mean, 74.4%), respectively. There were no significant differences between asthmatics and controls in LTC4 production stimulated by anti-FcepsilonRI antibody (P = .79), fMLP (P = .33) or PMA (P = .86). We found no correlation between stimulated LTC4 production and spirometric parameters at baseline or after bronchodilator administration or annual decline in FEV1%. CONCLUSION: Our results do not confirm the hypothesis that airway remodeling in asthma might be related to enhanced ability of leukocytes to produce cysteinyl leukotrienes in response to various stimuli.

Chromosomal aberrations and gene expression profiles in non-small cell lung cancer.

Alterations in genomic content and changes in gene expression levels are central characteristics of tumors and pivotal to the tumorigenic process. We analyzed 23 non-small cell lung cancer (NSCLC) tumors by array comparative genomic hybridization (array CGH). Aberrant regions identified included well-characterized chromosomal aberrations such as amplifications of 3q and 8q and deletions of 3p21.31. Less frequently identified aberrations such as amplifications of 7q22.3-31.31 and 12p11.23-13.2, and previously unidentified aberrations such as deletion of 11q12.3-13.3 were also detected. To enhance our ability to identify key acting genes residing in these regions, we combined array CGH results with gene expression profiling performed on the same tumor samples. We identified a set of genes with concordant changes in DNA copy number and expression levels, i.e. overexpressed genes located in amplified regions and underexpressed genes located in deleted regions. This set included members of the Wnt/beta-catenin pathway, genes involved in DNA replication, and matrix metalloproteases (MMPs). Functional enrichment analysis of the genes both overexpressed and amplified revealed a significant enrichment for DNA replication and repair, and extracellular matrix component gene ontology annotations. We verified the changes in expressions of MCM2, MCM6, RUVBL1, MMP1, MMP12 by real-time quantitative PCR. Our results provide a high resolution map of copy number changes in non-small cell lung cancer. The joint analysis of array CGH and gene expression analysis highlights genes with concordant changes in expression and copy number that may be critical to lung cancer development and progression.

Multiplexing schemes for generic SNP genotyping assays.

A generic genotyping assay utilizes a fixed set of reagents, which is independent of the actual target sample, to determine all present alleles. An example is the interrogation of several amplicons spanning polymorphic sites using an all k-mer array. Due to the high cost associated with a genotyping experiment, it is desirable to design a set of experiments, which maximizes the number of SNPs that can be genotyped in parallel per assay. In this study we investigate algorithmic approaches for optimally multiplexing SNP genotyping using generic assays. We devise a graph theoretic formulation of the problem and use it to derive an approximation algorithm for the problem, and several practical heuristics. We apply our methods to simulated and real data, for evaluating the multiplexing rates afforded by generic techniques. The results on real human data show the practicality of generic approaches for genotyping, allowing, e.g., the genotyping of 5000 SNPs using four all 7-mer arrays.

Analysis of expression patterns: the scope of the problem, the problem of scope.

Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics.

Lack of health insurance and decline in overall health in late middle age.

BACKGROUND: The number of adults in their 50s and 60s in the United States who do not have health insurance is increasing. This group may be particularly vulnerable to the ill effects of being uninsured. METHODS: We conducted a prospective cohort study using files from the Health and Retirement Study, a national survey of adults who were 51 to 61 years old in 1992. We determined the risks of a major decline in overall health and of the development of new physical difficulties between 1992 and 1996 for participants who were continuously uninsured (uninsured in 1992 and in 1994), those who were intermittently uninsured (uninsured either in 1992 or in 1994), and those who were continuously insured. We used logistic regression to determine the independent effects of being uninsured on health outcomes after adjustment for base-line sociodemographic factors, preexisting medical conditions, and types of health-related behavior such as smoking and alcohol use. RESULTS: We analyzed data for 7577 participants. The 717 continuously uninsured participants and the 825 intermittently uninsured participants were more likely than the 6035 continuously insured participants to have a major decline in overall health between 1992 and 1996 (21.6 percent, 16.1 percent, and 8.3 percent of the three groups, respectively; P<0.001 for both comparisons). According to a multivariate analysis, the adjusted relative risk of a major decline in overall health was 1.63 (95 percent confidence interval, 1.26 to 2.08) for continuously uninsured participants and 1.41 (95 percent confidence interval, 1.11 to 1.78) for intermittently uninsured participants, as compared with continuously insured participants. A new difficulty in walking or climbing stairs was also more likely to develop in the continuously or intermittently uninsured participants than in the continuously insured participants (28.8 percent, 26.4 percent, and 17.1 percent of the three groups, respectively; P<0.001 for both comparisons). The adjusted relative risk of such a new physical difficulty was 1.23 (95 percent confidence interval, 1.02 to 1.47) for the continuously uninsured participants and 1.26 (95 percent confidence interval, 1.01 to 1.54) for the intermittently uninsured participants. CONCLUSIONS: The lack of health insurance is associated with an increased risk of a decline in overall health among adults 51 to 61 years old.

On the complexity of positional sequencing by hybridization.

In sequencing by hybridization (SBH), one has to reconstruct a sequence from its l-long substrings. SBH was proposed as an alternative to gel-based DNA sequencing approaches, but in its original form the method is not competitive. Positional SBH (PSBH) is a recently proposed enhancement of SBH in which one has additional information about the possible positions of each substring along the target sequence. We give a linear time algorithm for solving PSBH when each substring has at most two possible positions. On the other hand, we prove that the problem is NP-complete if each substring has at most three possible positions. We also show that PSBH is NP-complete if the set of allowed positions for each substring is an interval of length k and provide a fast algorithm for the latter problem when k is bounded.

Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells.

The biochemical mechanisms underlying the inhibitory effects of lycopene, the main tomato carotenoid, on the growth of cancer cells are largely unknown. It has been hypothesized that lycopene derivatives may act as ligands for a nuclear receptor in analogy to retinoic acid, the hormone derived from beta-carotene. The inhibition of human mammary cancer (MCF-7) cell growth and the transactivation of the retinoic acid receptor (RAR) reporter gene by synthetic acyclo-retinoic acid, the open chain analog of retinoic acid, was compared to the effects of lycopene and retinoic acid in the same systems. Acyclo-retinoic acid activated the DR-5 retinoic acid response element with a approximately 100-fold lower potency than retinoic acid. This effect was independent of cotransfection with the RARalpha receptor. Lycopene exhibited only very modest activity in this system. In contrast to the results from the transactivation studies, acyclo-retinoic acid, retinoic acid, and lycopene inhibited cell growth with a similar potency. Preincubation with each of the three compounds slowed down cell cycle progression from G1 to S phase. In summary, acyclo-retinoic acid inhibited cancer cell growth and interacted with RAR. However, it exhibited low affinity for RAR and a correspondingly low efficacy in activating this receptor, indicating that RAR does not mediate the growth inhibitory effect of the compound. In addition, the concentrations of acyclo-retinoic acid and of lycopene required for inducing inhibition of cell growth were similar, suggesting that acyclo-retinoic acid is unlikely to be the active metabolite of lycopene.

Morbidity and cost implications of inadequate hemodialysis.

American hemodialysis patients have short lifespans, frequent hospitalizations, and aggregate Medicare inpatient expenditures of $4 billion/year. Dose of dialysis, as quantified by the parameter, Kt/V, corresponds strongly with survival and is estimated to be inadequate (Kt/V <1.2) in one fourth of patients. However, little is known about the morbidity and cost implications of inadequate dialysis. We sought to determine the independent relationship between dose of dialysis and (1) number of hospitalizations, (2) hospital days, and (3) Medicare inpatient reimbursements. We randomly selected 674 patients from all 22 hemodialysis units in northeast Ohio and examined hospitalizations, hospital days, and Medicare inpatient reimbursements for a 6-month interval following a 90-day quantification of dialysis dose. Every 0.1 decrease in Kt/V was independently associated with more hospitalizations (rate ratio, 1.11; 95% confidence interval [CI], 1.07 to 1.15), increased hospital days (rate ratio, 1.12; 95% CI, 1.03 to 1.22), and higher Medicare inpatient expenditures ($940; 95% CI, $450 to $1,440) after adjustment for patient age, sex, race, cause of renal failure, number of years on dialysis, and number of comorbid conditions. We estimate that increasing dialysis doses to a Kt/V of 1.2 for all patients nationally may decrease Medicare inpatient expenditures by $150 million annually. In conclusion, inadequate dialysis dose is independently associated with increased hospitalizations, hospital days, and Medicare inpatient expenditures. Improving dialysis adequacy may both improve patient morbidity and lessen health care costs.

Gene-expression profiles in hereditary breast cancer.

BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.

Enhanced-resolution image restoration from a sequence of low-frequency vibrated images by use of convex projections.

An algorithm to increase the spatial resolution of digital video sequences captured with a camera that is subject to mechanical vibration is developed. The blur caused by vibration of the camera is often the primary cause for image degradation. We address the degradation caused by low-frequency vibrations (vibrations for which the exposure time is less than the vibration period). The blur caused by low-frequency vibrations differs from other types by having a random shape and displacement. The different displacement of each frame makes the approach used in superresolution (SR) algorithms suitable for resolution enhancement. However, SR algorithms that were developed for general types of blur should be adapted to the specific characteristics of low-frequency vibration blur. We use the method of projection onto convex sets together with a motion estimation method specially adapted to low-frequency vibration blur characteristics. We also show that the random blur characterizing low-frequency vibration requires selection of the frames prior to processing. The restoration performance as well as the frame selection criteria is dependent mainly on the motion estimation precision.

Universal DNA tag systems: a combinatorial design scheme.

Custom-designed DNA arrays offer the possibility of simultaneously monitoring thousands of hybridization reactions. These arrays show great potential for many medical and scientific applications, such as polymorphism analysis and genotyping. Relatively high costs are associated with the need to specifically design and synthesize problem-specific arrays. Recently, an alternative approach was suggested that utilizes fixed, universal arrays. This approach presents an interesting design problem-the arrays should contain as many probes as possible, while minimizing experimental errors caused by cross-hybridization. We use a simple thermodynamic model to cast this design problem in a formal mathematical framework. Employing new combinatorial ideas, we derive an efficient construction for the design problem and prove that our construction is near-optimal.

Tissue classification with gene expression profiles.

Constantly improving gene expression profiling technologies are expected to provide understanding and insight into cancer-related cellular processes. Gene expression data is also expected to significantly aid in the development of efficient cancer diagnosis and classification platforms. In this work we examine three sets of gene expression data measured across sets of tumor(s) and normal clinical samples: The first set consists of 2,000 genes, measured in 62 epithelial colon samples (Alon et al., 1999). The second consists of approximately equal to 100,000 clones, measured in 32 ovarian samples (unpublished extension of data set described in Schummer et al. (1999)). The third set consists of approximately equal to 7,100 genes, measured in 72 bone marrow and peripheral blood samples (Golub et al, 1999). We examine the use of scoring methods, measuring separation of tissue type (e.g., tumors from normals) using individual gene expression levels. These are then coupled with high-dimensional classification methods to assess the classification power of complete expression profiles. We present results of performing leave-one-out cross validation (LOOCV) experiments on the three data sets, employing nearest neighbor classifier, SVM (Cortes and Vapnik, 1995), AdaBoost (Freund and Schapire, 1997) and a novel clustering-based classification technique. As tumor samples can differ from normal samples in their cell-type composition, we also perform LOOCV experiments using appropriately modified sets of genes, attempting to eliminate the resulting bias. We demonstrate success rate of at least 90% in tumor versus normal classification, using sets of selected genes, with, as well as without, cellular-contamination-related members. These results are insensitive to the exact selection mechanism, over a certain range.

Molecular classification of cutaneous malignant melanoma by gene expression profiling.

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

RHO--radiation hybrid ordering.

Radiation hybrid (RH) mapping is a somatic cell technique that is used for ordering markers along a chromosome and estimating the physical distances between them. With the advent of this mapping technique, analyzing the experimental data is becoming a challenging and demanding computational task. In this paper we present the software package RHO (radiation hybrid ordering). The package implements a number of heuristics that attempt to order genomic markers along a chromosome, given as input the results of an RH experiment. The heuristics are based on reducing an appropriate optimization problem to the traveling salesman problem (TSP). The reduced optimization problem is either the nonparametric obligate chromosome breaks (OCBs) or the parametric maximum likelihood estimation (MLE). We tested our package on both simulated and publicly available RH data. For synthetic RH data, the reconstructed markers' permutation is very close to the original permutation, even with fairly high error rates. For real data we used the framework markers' data from the Whitehead Institute maps. For most of the chromosomes (18 out of 23), there is a perfect agreement or nearly perfect agreement (reversal of chromosome arm or arms) between our maps and the Whitehead framework maps. For the remaining five chromosomes, our maps improve on the Whitehead framework maps with respect to both optimization criteria, having higher likelihood and fewer breakpoints. For three chromosomes, the results differ significantly (lod score >1.75), with chromosome 2 having the largest improvement (lod score 3.776).

Clustering gene expression patterns.

Recent advances in biotechnology allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. Analysis of data produced by such experiments offers potential insight into gene function and regulatory mechanisms. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. The corresponding algorithmic problem is to cluster multicondition gene expression patterns. In this paper we describe a novel clustering algorithm that was developed for analysis of gene expression data. We define an appropriate stochastic error model on the input, and prove that under the conditions of the model, the algorithm recovers the cluster structure with high probability. The running time of the algorithm on an n-gene dataset is O[n2[log(n)]c]. We also present a practical heuristic based on the same algorithmic ideas. The heuristic was implemented and its performance is demonstrated on simulated data and on real gene expression data, with very promising results.

[Comparison of exercise and histamine provocation tests in patients with bronchial asthma]. / Porównanie prób prowokacyjnych wysilkowej i histaminowej u chorych na astme oskrzelowa.

Fifty-eight asthmatic patients (22 men and 36 women), aged 17 to 61 years, participated in this study. Thirty-two of them had atopic asthma. Exercise test and histamine inhalation challenge test were performed in all subjects. Patients exercised on a bicycle ergometer for 6-8 min. to increase the heart rate to 80% of predicted maximal heart rate. Twenty-three patients had a bronchospasm following exercise. The PC20 values in patients with exercise induced asthma (Me = 0.35 mg/ml) were significantly lower (p = 0.006) than in subjects without exercise induced asthma (Me = 1.89 mg/ml). There was low but statistically significant correlation between PC20 and delta FEV1 after exercise (R(s) = 0.32; p = 0.01). These results suggest that there are not only similarities but also differences in pathomechanisms of bronchial hyperreactivity to histamine and exercise-induced bronchoconstriction. The lack of statistically significant correlation between diurnal PEF variation and PC20 values suggest that the former parameter cannot be considered as an useful marker of nonspecific bronchial hyperreactivity.

Practice patterns, case mix, Medicare payment policy, and dialysis facility costs.

OBJECTIVE: To evaluate the effects of case mix, practice patterns, features of the payment system, and facility characteristics on the cost of dialysis. DATA SOURCES/STUDY SETTING: The nationally representative sample of dialysis units in the 1991 U.S. Renal Data System's Case Mix Adequacy (CMA) Study. The CMA data were merged with data from Medicare Cost Reports, HCFA facility surveys, and HCFA's end-stage renal disease patient registry. STUDY DESIGN: We estimated a statistical cost function to examine the determinants of costs at the dialysis unit level. PRINCIPAL FINDINGS: The relationship between case mix and costs was generally weak. However, dialysis practices (type of dialysis membrane, membrane reuse policy, and treatment duration) did have a significant effect on costs. Further, facilities whose payment was constrained by HCFA's ceiling on the adjustment for area wage rates incurred higher costs than unconstrained facilities. The costs of hospital-based units were considerably higher than those of freestanding units. Among chain units, only members of one of the largest national chains exhibited significant cost savings relative to independent facilities. CONCLUSIONS: Little evidence showed that adjusting dialysis payment to account for differences in case mix across facilities would be necessary to ensure access to care for high-cost patients or to reimburse facilities equitably for their costs. However, current efforts to increase dose of dialysis may require higher payments. Longer treatments appear to be the most economical method of increasing the dose of dialysis. Switching to more expensive types of dialysis membranes was a more costly means of increasing dose and hence must be justified by benefits beyond those of higher dose. Reusing membranes saved money, but the savings were insufficient to offset the costs associated with using more expensive membranes. Most, but not all, of the higher costs observed in hospital-based units appear to reflect overhead cost allocation rather than a difference in real resources devoted to treatment. The economies experienced by the largest chains may provide an explanation for their recent growth in market share. The heterogeneity of results by chain size implies that characterizing units using a simple chain status indicator variable is inadequate. Cost differences by facility type and the effects of the ongoing growth of large chains are worthy of continued monitoring to inform both payment policy and antitrust enforcement.