A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia.

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.

Service utilization in Medicaid HIV specialty plans versus standard plans among enrollees diagnosed with HIV/AIDS in Florida, U.S.A.

In the United States (U.S.), to contain costs many state Medicaid programs offer specialty health insurance plans for costly conditions such as HIV/AIDS. This study compared service utilization between Florida Medicaid enrollees diagnosed with HIV/AIDS in standard Medicaid managed care plans to enrollees in HIV/AIDS specialty plans. We found lower mean utilization among HIV/AIDS enrollees in specialty plans compared to enrollees with HIV/AIDS in standard MMA plans for all services except inpatient which was approximately the same. While fewer emergency visits is a desired outcome, lower rates of other services may indicate suboptimal management of patients or lower engagement in care among enrollees in HIV/AIDS specialty plans. Continuous monitoring of experiences of patients in HIV/AIDS specialty plans is warranted to determine whether the observed utilization patterns represent better management through reductions in low value care or reduced engagement in care, and whether these utilization patterns persist.

Role of Prices, Utilization, and Health in Explaining Texas Medicaid Newborn Care Spending Variation.

BACKGROUND: Newborn care is one of the most frequent types of hospitalization and Medicaid covers over 50% of all births nationwide. However, little is known about regional variation in Medicaid newborn care spending and its drivers. OBJECTIVES: To measure the contribution of market-level prices, utilization, and health risk on regional variation in spending among newborn Medicaid population in Texas. RESEARCH DESIGN AND METHODS: The study used 2014 Texas Medicaid newborn claims and encounters linked to birth and death certificate data. Newborn care spending was defined as Medicaid payments per newborn hospital stay, including hospital transfers, from birth through discharge home or death. Spending was further categorized into inpatient facility and related professional spending. Variation in spending across neonatal intensive care regions was decomposed into price and utilization, accounting for input price and health risk differences. RESULTS: Newborn care spending across Texas regions varied significantly (coefficient of variation, 0.31), with most of the variation attributed to spending on inpatient facility services (91%). Both price (41%) and utilization (27%) played a role in explaining this variation, after adjusting for health status (29%) and input price (4%). Though most regions with the highest spending indexes had high price and utilization indexes, some had high spending driven mostly by high prices and others by high utilization. CONCLUSIONS: Significant regional variations in price, utilization, and health status exist in Medicaid newborn care across Texas in 2014. Disentangling the effect of each driver is important to address spending variation and improve efficiency in newborn care.

The wellness incentives and navigation project: design and methods.

BACKGROUND: About 35 % of non-elderly U.S. adult Medicaid enrollees have a behavioral health condition, such as anxiety, mood disorders, substance use disorders, and/or serious mental illness. Individuals with serious mental illness, in particular, have mortality rates that are 2 to 3 times higher as the general population, which are due to multiple factors including inactivity, poor nutrition, and tobacco use. 61 % of Medicaid beneficiaries with behavioral health conditions also have multiple other co-occurring chronic physical health conditions, which further contributes to morbidity and mortality. The Wellness Incentives and Navigation (WIN) project is one of 10 projects under the Centers for Medicare and Medicaid Services "Medicaid Incentives for the Prevention of Chronic Diseases" Initiative, to "test the effectiveness of providing incentives directly to Medicaid beneficiaries of all ages who participate in prevention programs, and change their health risks and outcomes by adopting healthy behaviors." METHODS/DESIGN: WIN is a three-year randomized pragmatic clinical trial designed to examine the comparative effectiveness of the combined use of personal navigators, motivational interviewing, and a flexible wellness account on cardiovascular risk reduction among individuals in Medicaid with co-occurring physical and mental health conditions or serious mental illness alone relative to the usual care provided within Medicaid Managed Care. 1250 individuals, identified through Medicaid claims data, were recruited and randomly assigned to an intervention group or control group with outcomes tracked annually. A comparison group was also recruited to help assess the study's internal validity. DISCUSSION: The primary outcomes are physical and mental health related quality-of-life as measured by the SF-12, and BMI, blood pressure, LDL-C, and Hba1c results for those who are diabetic measured clinically. The purpose of this paper is to present the unique design of the WIN trial prior to results becoming available in hopes of assisting other researchers in conducting community-based randomized pragmatic trials. Outcomes will be assessed through the linkage of patient reported outcomes, health care claims, and electronic health record data. TRIAL REGISTRATION: NCT02440906.

Distinct regions within fibulin-1D modulate interactions with hemicentin.

Fibulins are evolutionarily conserved extracellular matrix (ECM) proteins that assemble in elastic fibers and basement membranes. Caenorhabditis elegans has a single fibulin gene that produces orthologs of vertebrate fibulin-1 C and D splice forms. In a structure-function analysis of fibulin-1 domains, a series of deletion constructs show that EGF repeats 4 and 5 are required for the hemicentin-dependent assembly and function of fibulin-1D in native locations. In contrast, constructs missing the second EGF repeat of fibulin-1D (EGF2D) assemble in ectopic locations in a hemicentin dependent manner. Constructs that contain EGF2D are cleaved into two fragments, but constructs with EGF2D missing are not, suggesting that a protease binds and/or cleaves fibulin-1D at a site that is likely within EGF2D. Together, the data suggests that EGF repeats 4 and 5 promote interaction with hemicentin while a region within EGF2D suppresses ectopic interactions with hemicentin and this suppression may be protease dependent.

The use and misuse of thrombolytic therapy within the Veterans Health Administration.

BACKGROUND: Within the Veterans Health Administration (VHA), approximately 6000 veterans are hospitalized with acute ischemic stroke annually. We examined the use and misuse of thrombolytic therapy with tissue plasminogen activator (tPA) in a national sample of veterans who were admitted to a VHA Medical Center (VAMC) with acute ischemic stroke. METHODS: Medical record reviews were conducted on 5000 acute stroke patients who were admitted to a VAMC in 2007. Patients were defined as eligible to receive tPA if they arrived at the hospital within 3 hours of stroke symptom onset and had no contraindications to tPA. We compared eligible patients who received tPA to those who did not and examined the distribution of eligible patients across the 129 VAMCs included in this study. RESULTS: Among the 3931 ischemic stroke patients, 174 (4.4%) were eligible for tPA. Among the 135 patients who arrived within 2 hours of symptom onset which allowed adequate time for testing and evaluation, 19 (14.1%) received tPA. An additional 11 patients received tPA but did not meet eligibility criteria. Eligible patients receiving tPA were similar to eligible patients not receiving tPA in terms of clinical conditions and time to brain imaging. Among the 30 patients that received tPA, 5 (16.6%) received the wrong dose. Among the 85 VAMCs that received ≥1 eligible patient, on average 2.3 patients were eligible for tPA annually. CONCLUSIONS: Relatively few eligible veterans receive thrombolysis across the VHA system. Strategies to improve thrombolysis delivery will have to account for the low annual volume of eligible stroke patients cared for at individual VAMCs.

A Nonclassical Mechanism of ß-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus and Its Effect on Virulence.

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of pathogenic bacteria that are infamously resistant to ß-lactam antibiotics, a property attributed to the mecA gene. Recent studies have reported that mutations associated with the promoter region of pbp4 demonstrated high levels of ß-lactam resistance, suggesting the role of PBP4 as an important non-mecA mediator of ß-lactam resistance. The pbp4-promoter-associated mutations have been detected in strains with or without mecA. Our previous studies that were carried out in strains devoid of mecA described that pbp4-promoter-associated mutations lead to PBP4 overexpression and ß-lactam resistance. In this study, by introducing various pbp4-promoter-associated mutations in the genome of a MRSA strain, we demonstrate that PBP4 overexpression can supplement mecA-associated resistance in S. aureus and can lead to increased ß-lactam resistance. The promoter and regulatory region of pbp4 is shared with a divergently transcribed gene, abcA, which encodes a multidrug exporter. We demonstrate that the promoter mutations caused an upregulation of pbp4 and downregulation of abcA, confirming that the resistant phenotype is associated with PBP4 overexpression. PBP4 has also been associated with staphylococcal pathogenesis, however, its exact role remains unclear. Using a Caenorhabditis elegans model, we demonstrate that strains having increased PBP4 expression are less virulent than wild-type strains, suggesting that ß-lactam resistance mediated via PBP4 likely comes at the cost of virulence. IMPORTANCE Our study demonstrates the ability of PBP4 to be an important mediator of ß-lactam resistance in not only methicillin-susceptible Staphylococcus aureus (MSSA) background strains as previously demonstrated but also in MRSA strains. When present together, PBP2a and PBP4 overexpression can produce increased levels of ß-lactam resistance, causing complications in treatment. Thus, this study suggests the importance of monitoring PBP4-associated resistance in clinical settings, as well as understanding the mechanistic basis of associated resistance, so that treatments targeting PBP4 may be developed. This study also demonstrates that S. aureus strains with increased PBP4 expression are less pathogenic, providing important hints about the role of PBP4 in S. aureus resistance and pathogenesis.

Participation of older patients with prostate cancer in Medicare eligible trials.

PURPOSE: On June 7, 2000 President Clinton issued an executive memorandum directing Medicare payment for routine patient care in qualifying clinical trials. We estimated the proportion of older patients with prostate cancer who were examined as part of a qualifying clinical trial, and the association between participation and patient characteristics. MATERIALS AND METHODS: We performed an observational study using the Surveillance, Epidemiology and End Results Medicare database to determine participation in qualifying clinical trials in a sample of 37,216 men 66 years old or older who were enrolled in Medicare and diagnosed with prostate cancer between September 2000 and December 2002. RESULTS: Within 3 years of diagnosis 211 men (0.567%) received routine patient care in a qualifying clinical trial. These participants were more likely to be younger than 70 years (OR 1.687, 95% CI 1.27-2.24) and less likely to be less educated and reside in low income, metropolitan neighborhoods. White men were more likely to participate in clinical trials than nonwhite men but this association was not statistically significant (OR 1.426, CI 0.97-2.09). Participation varied significantly by registry site (0% to 1.2%) but not by tumor grade or stage, or prostate specific antigen status. CONCLUSIONS: Few older patients with prostate cancer participated in qualifying trials between 2000 and 2002. Those who participated were not representative of the general population of older patients with prostate cancer. Greater efforts are required to expand trial enrollment and decrease disparities in research participation.

Cost, utilization, and policy of provision of assistive technology devices to veterans poststroke by Medicare and VA.

BACKGROUND: The increase in provision of assistive technology devices (ATDs) has spurred controversy over Medicare policy aimed at reducing cost-policy that forces social isolation and conflicts with legislation, facilitating participation for individuals with disabilities. In contrast, Department of Veterans Affairs (VA) policy does not limit provision of AT to "in home" use only but rather, states "all enrolled and some non-enrolled veterans are eligible for all needed prosthetics." OBJECTIVES: Examine ATD provision policy by comparing 2 systems, Medicare and VA. Empirically analyze differences in ATDs provided, cost, and duplication in provision. RESEARCH DESIGN: Retrospective study of VA databases, including VA Medicare data. SUBJECTS: A population based study of 12,0461 veterans post-stroke. MEASURES: Frequency of provision of ATDs by Health Care Common Procedural Code, purchase price, and capped rental payments. RESULTS: Of the poststroke veteran cohort, 39% received no AT, 56% received AT from the VA only, 1% received AT from Medicare only, and 3% received AT from both the VA and Medicare. Most ATDs were for activities of daily living, followed by walkers/canes/crutches. In specific ATD comparisons, VA costs were substantially lower than Medicare for purchased items and slightly lower than Medicare for capped rental payments. CONCLUSION: VA provides a broader variety of ATDs at a lesser cost than Medicare. Analyses of policy differences between VA and Medicare suggest VA policy is driven by veteran need whereas Medicare policy is driven at least in part, by containing costs that have skyrocketed as a result of fraudulent claims.

Demographic and clinical variation in Veterans Health Administration provision of assistive technology devices to veterans poststroke.

OBJECTIVES: To examine variation in provision of assistive technology (AT) devices and the extent to which such variation may be explained by patient characteristics or Veterans Health Administration (VHA) administrative region. DESIGN: Retrospective population-based study. SETTING: VHA. PARTICIPANTS: Veterans poststroke in fiscal years 2001 and 2002 (N=12,046). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Provision of 8 categories of AT devices. RESULTS: There was considerable regional variation in provision of AT. For example, differences across administrative regions in the VHA ranged from 5.1 to 28.1 standard manual wheelchairs per 100 veterans poststroke. Using logistic regression, with only demographic variables as predictors of standard manual wheelchair provision, the c statistic was .62, and the pseudo R(2) was 2.5%. Adding disease severity increased the c statistic to .67 and the pseudo R(2) to 6.2%, and adding Veteran Integrated Network System further increased the c statistic to .72 and pseudo R(2) to 9.8%. CONCLUSIONS: Our research showed significant variation in the provision of AT devices to veterans poststroke, and it showed that patient characteristics accounted for only 6.2% of the variation. VHA administrative region and disability severity accounted for equivalent amounts of the variation. Our findings suggest the need for improvements in the process for providing AT and/or provider education concerning device provision.

Early administration of steroids in the ambulance setting: Protocol for a type I hybrid effectiveness-implementation trial with a stepped wedge design.

BACKGROUND: Pediatric asthma exacerbations are a frequent reason for emergency care. Early administration of oral systemic corticosteroids (OCS) in the emergency department (ED) decreases hospitalization rates and ED length-of-stay (LOS). However, it is unknown whether even earlier OCS administration by emergency medical services (EMS) in the prehospital setting further improves outcomes. PURPOSE: To describe the background and methods of a type 1 hybrid effectiveness-implementation trial of EMS-administered OCS for pediatric asthma patients incorporating a stepped wedge design and the RE-AIM framework. METHODS: The study employs a non-randomized stepped wedge design where multiple EMS agencies adopt OCS as a treatment for pediatric asthma exacerbations at varying times. This design accommodates ethical considerations of studying pediatric subjects in the prehospital setting where informed consent is not feasible. We will compare hospitalization rates, ED LOS, and short-term healthcare costs between pediatric asthma patients who do and do not receive OCS from EMS. Using geographic information systems (GIS), we will measure how differences in outcomes scale with increasing EMS transport time. We will use the RE-AIM framework to guide a mixed methods analysis of barriers and enablers to EMS administration of OCS for pediatric asthma patients, including quantitative measures of adoption and uptake and qualitative EMS provider focus group data. CONCLUSION: This trial will determine if earlier EMS administration of OCS to pediatric asthma patients decreases hospitalizations, ED LOS, and short-term healthcare costs, and if those outcomes scale with longer EMS transport times. We will identify barriers and enablers to implementing EMS-administered OCS for pediatric asthma patients.

Overexpression of human Atp13a2Isoform-1 protein protects cells against manganese and starvation-induced toxicity.

Mutations in ATP13A2 cause Kufor-Rakeb syndrome (KRS), a juvenile form of Parkinson's disease (PD) with dementia. However, the mechanisms by which mutations in ATP13A2 cause KRS is not understood. The mutations lead to misfolding of the translated Atp13a2 protein and its premature degradation in the endoplasmic reticulum, never reaching the lysosome where the protein is thought to function. Atp13a2 is a P-type ATPase, a class of proteins that function in ion transport. Indeed, studies of human, mouse, and yeast Atp13a2 proteins suggest a possible involvement in regulation of heavy metal toxicity. Here we report on the cytoprotective function of Atp13a2 on HeLa cells and dopamine neurons of Caenorhabditis elegans (C. elegans). HeLa cells stably overexpressing V5- tagged Atp13a2Isoform-1 protein were more resistant to elevated manganese exposure and to starvation-induced cell death compared to cells not overexpressing the protein. Because PD is characterized by loss of dopamine neurons, we generated transgenic C. elegans expressing GFP-tagged human Atp13a2 protein in dopamine neurons. The transgenic animals exhibited higher resistance to dopamine neuron degeneration after acute exposure to manganese compared to nematodes that expressed GFP alone. The results suggest Atp13a2 Isoform-1 protein confers cytoprotection against toxic insults, including those that cause PD syndromes.

Visits to Primary Care and Emergency Department Reliance for Foster Youth: Impact of Medicaid Managed Care.

OBJECTIVE: To examine the rate of access to primary and preventive care and emergency department (ED) reliance for foster youth as well as the impact of a transition from fee-for-service (FFS) Medicaid to managed care (MC) on this access. METHODS: Secondary administrative data were obtained from Medicaid programs in one state that transitioned foster youth from an FFS to an MC (Texas) and another state, comparable in population size and racial/ethnic diversity, which continuously enrolled foster youth in an FFS system (Florida). Eligible participants were foster youth (aged 0-18 years) enrolled in these states between 2006 and 2010 (n = 126,714). A Puhani approach to difference-in-difference was used to identify the effect of transition after adjusting for race/ethnicity, gender, and health status. Data were used to calculate access to primary and preventive care as well as ED reliance. ED reliance was operationalized as the number of ED visits relative to the number of total ambulatory visits; high ED reliance was defined as ≥33%. RESULTS: The transition to MC was associated with a 6% to 13% increase in access to primary care. Preventive care visits were 10% to 13% higher among foster youth in MC compared to those in FFS. ED reliance declined for the intervention group but to a lesser extent than did the control group, yielding a positive mean percentage change. CONCLUSIONS: Foster youth access to care may benefit from a Medicaid MC delivery system, particularly as the plans used are designed with the unique needs of this vulnerable population.

Hemicentins assemble on diverse epithelia in the mouse.

Hemicentins are recently described extracellular matrix (ECM) proteins with a single ortholog in C. elegans that assembles into discrete tracks constricting broad regions of epithelial cell contact into adhesive and flexible line-shaped junctions. There are two highly conserved hemicentin genes in most vertebrate species; however, nothing is known about the function or distribution of vertebrate hemicentins. To determine the distribution of vertebrate hemicentins, we used a polyclonal antibody to stain mouse tissue and showed that hemicentins are found in the pericellular ECM of epithelial cells in a number of tissues including embryonic trophectoderm and adult skin and tongue, in addition to the ECM of some, but not all, blood vessels. Hemicentins also assemble on multiple epithelia in the eye, including cornea, lens, and retina. The pericellular localization of vertebrate hemicentins on epithelia and other cell surfaces suggests that vertebrate hemicentins, like their nematode counterpart, are secreted ECM proteins likely to have a role in the architecture of adhesive and flexible cell junctions, particularly in tissues subject to significant amounts of mechanical stress.

Persistence of high health care expenditures among children in Medicaid.

Cross-sectional studies show that a small percentage of children consume a large portion of the health care dollar. However, little is known about the persistence of high health care expenditures among children enrolled in Medicaid health maintenance organizations (HMOs) or in primary care case management (PCCM) programs. This study found substantial expenditure persistence during a 3-year period. Among Temporary Aid to Needy Families (TANF) children in HMOs in the top 10 percent of the expenditure distribution in 2003, 34 percent remained in the top 10 percent in 2004, and 23 percent remained in the top 10 percent in 2005. Similar patterns were observed for TANF children in the PCCM. Expenditure persistence varied based on the enrollees' enabling and need characteristics, providing opportunities to identify children with high health care expenditures who may benefit from care coordination.

Missing data on the Center for Epidemiologic Studies Depression Scale: a comparison of 4 imputation techniques.

BACKGROUND: Missing data are widespread in the medical sciences. Given their prevalence, researchers must be prepared to address problems that arise when data are missing. OBJECTIVES: The objectives were to (1) provide an estimate of bias for each imputation technique with known values from data engineered to be missing completely at random; (2) determine whether different Center for Epidemiologic Studies Depression (CES-D) Scale scores were obtained from item-mean, person-mean, regression, and hot-deck imputation techniques and whether they differed from the CES-D score obtained from complete cases; and (3) determine whether the variables that predicted the CES-D scores were the same for the complete cases and each of the 4 imputation techniques. METHODS: Depressive symptoms were assessed in patients (N=2,317) in an international clinical trial comparing high blood pressure treatments between April 1, 1999, and October 31, 1999. Patients were mailed surveys after randomization. Depressive symptoms were measured using the CES-D Scale. Respondents who completed all 20 items were compared with those who did not complete all 20 items, using independent t tests and chi-square. Z scores were used to determine CES-D mean differences, and multiple regression models were used to predict the CES-D scores for the 4 imputation techniques and the complete case data. RESULTS: Imputed CES-D mean scores ranged from 14.58 to 14.68. The 4 imputed CES-D mean scores were consistently, but not significantly, higher than the complete case CES-D mean of 14.06. Imputed mean scores were similar to each other and the complete case mean score. Four regression models predicting the imputed CES-D scores yielded similar predictions. With the exception of sex, the same variables predicted the complete case CES-D and the imputed CES-D scores. CONCLUSIONS: All the imputed means were similar to the complete case mean, with the exception of the regression imputation. Imputing missing data did not significantly alter the conclusions regarding which factors were associated with variations in CES-D scores. Since imputation has the potential to increase statistical power, researchers dealing with missing CES-D scores should consider imputing missing data.

Variation in outpatient emergency department utilization in Texas Medicaid: a state-level framework for finding "superutilizers".

BACKGROUND: Very frequent outpatient emergency department (ED) use-so called "superutilization"-at the state level is not well-studied. To address this gap, we examined frequent ED utilization in the largest state Medicaid population to date. METHODS: Using Texas Medicaid (the third largest in the USA) claims data, we examined the variability in expenditures, sociodemographics, comorbidities, and persistence across seven levels of ED utilization/year (i.e., 1, 2, 3-4, 5-6, 7-9, 10-14, and ≥ 15 visits). We classified visits into emergent and non-emergent categories using the most recent New York University algorithm. RESULTS: Thirty-one percent (n = 346,651) of Texas Medicaid adult enrollees visited the ED at least once in 2014. Enrollees with ≥ 3 ED visits accounted for 8.5% of all adult patients, 60.4% of the total ED visits, and 62.1% of the total ED expenditures. Extremely frequent ED users (≥ 10 ED visits) represented < 1% of all users but accounted for 15.5% of all ED visits and 17.4% of the total ED costs. The proportions of ED visits classified as non-emergent or emergent, but primary care treatable varied little as ED visits increased. Overall, approximately 13% of ED visits were considered not preventable or avoidable. CONCLUSIONS: The Texas Medicaid population has a substantial burden of chronic disease with only modest increases in substance use and mental health diagnoses as annual visits increase. Understanding the characteristics that lead to frequent ED use is vital to developing strategies and Medicaid policy to reduce high utilization.

Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus.

Over 170 different mutations in the gene encoding SOD1 all cause amyotrophic lateral sclerosis (ALS). Available studies have been primarily focused on the mechanisms underlying mutant SOD1 cytotoxicity. How cells defend against the cytotoxicity remains largely unknown. Here, we show that misfolding of ALS-linked SOD1 mutants and wild-type (wt) SOD1 exposes a normally buried nuclear export signal (NES)-like sequence. The nuclear export carrier protein CRM1 recognizes this NES-like sequence and exports misfolded SOD1 to the cytoplasm. Antibodies against the NES-like sequence recognize misfolded SOD1, but not native wt SOD1 both in vitro and in vivo. Disruption of the NES consensus sequence relocalizes mutant SOD1 to the nucleus, resulting in higher toxicity in cells, and severer impairments in locomotion, egg-laying, and survival in Caenorhabditis elegans. Our data suggest that SOD1 mutants are removed from the nucleus by CRM1 as a defense mechanism against proteotoxicity of misfolded SOD1 in the nucleus.

The effects of reinsurance in financing children's health care.

This paper examines the effects of reinsurance on the financial performance of health plans serving enrollees in a State Children's Health Insurance Program (SCHIP). We demonstrate that simple reinsurance policies can reduce substantially the variation in the financial performance of plans with different case mixes, even when the plans bear the cost of the reinsurance and are not fully insured against large expenditures on individual enrollees.

Disenrollment and re-enrollment patterns in a SCHIP.

This article examines the impact of four policy changes made to a State children's health insurance program (SCHIP) as it transitioned to Title XXI on program disenrollment and re-enrollment. The changes were: (1) expanded eligibility criteria, (2) reduction in the family share of the premium, (3) expansion of the mental health benefit, and (4) implementation of a 60-day wait period to re-enrollment in the program for children who involuntarily disenrolled due in non-payment of premium. Disenrollment was reduced by 20 percent after the changes were implemented. Disenrollment and re-enrollment rates varied significantly based on the child's health and family income.