Local Residential Sorting and Public Goods Provision: A Classroom Demonstration

This classroom exercise illustrates the Tiebout (1956) hypothesis that residential sorting across multiple jurisdictions leads to a more efficient allocation of local public goods. The exercise places students with heterogeneous preferences over a public good into a single classroom community. A simple voting mechanism determines the level of public good provision in the community. Next, the classroom is divided in two, and students may choose to move between the two smaller communities, sorting themselves according to their preferences for public goods. The exercise places cost on movement at first, then allows for costless sorting. Students have the opportunity to observe how social welfare rises through successive rounds of the exercise, as sorting becomes more complete. They may also observe how immobile individuals can become worse off because of incomplete sorting when the Tiebout assumptions do not hold perfectly

Custom-molded foot-orthosis intervention and multi-segment medial foot kinematics during walking

Context: Foot-orthosis (FO) intervention to prevent and treat numerous lower extremity injuries is widely accepted clinically. However, the results of quantitative gait analyses have been equivocal. The foot models used, participants receiving intervention, and orthoses used might contribute to the variability. Objective: To investigate the effect of a custom-molded FO intervention on multisegment medial foot kinematics during walking in participants with low-mobile foot posture. Design: Crossover study. Setting: University biomechanics and ergonomics laboratory. Patients or Other Participants: Sixteen participants with low-mobile foot posture (7 men, 9 women) were assigned randomly to 1 of 2 FO groups. Intervention(s): After a 2-week period to break in the FOs, individuals participated in a gait analysis that consisted of 5 successful walking trials (1.3 to 1.4 m/s) during no-FO and FO conditions. Main Outcome Measure(s): Three-dimensional displacements during 4 subphases of stance (loading response, mid- stance, terminal stance, preswing) were computed for each multisegment foot model articulation. Results: Repeated-measures analyses of variance (ANO- VAs) revealed that rearfoot complex dorsiflexion displacement during midstance was greater in the FO than the no-FO condition (F114 = 5.24, P=.O4, partial r|2 = 0.27). Terminal stance repeated-measures ANOVA results revealed insert-by-insert condition interactions for the first metatarsophalangeal ¡oint complex (F114=7.87, P=.O1, partial if = 0.36). However, additional follow-up analysis did not reveal differences between the no-FO and FO conditions for the balanced traditional ortho- sis (F, 14 = 4.32, P = .O8, partial if = 0.38) or full-contact orthosis (F1i14 = 4.10, P=.O8, partial if = 0.37). Conclusions: Greater rearfoot complex dorsiflexion during midstance associated with FO intervention may represent improved foot kinematics in people with low-mobile foot postures. Furthermore, FO intervention might partially correct dysfunctional kinematic patterns associated with low-mobile foot postures.

Purkinje cell loss in experimental autoimmune encephalomyelitis

Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease

Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem.

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids

Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance

The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alpha–beta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Direct Economic Losses in the Northridge Earthquake: A Three-Year Post-Event Perspective

The Northridge earthquake will long be remembered for the unprecedented losses incurred as a result of a moderate-size event in a suburban area of Los Angeles. Current documented costs indicate that this event is the costliest disaster in U.S. history. Although it is difficult to estimate the full cost of this event, it is quite possible that total losses, excluding indirect effects, could reach as much as $40 billion. This would make the Northridge earthquake less severe than the Kobe event, which occurred exactly one year after the Northridge earthquake, but adds a bit of realism that a Kobe-type disaster is possible in the U.S. This paper attempts to put into perspective the direct capital losses associated with the Northridge earthquake. In doing so, we introduce the concept of hidden and/or undocumented costs that could double current estimates. In addition, we present the notion that a final estimate of loss may be impossible to achieve, although costs do begin to level off two years after the earthquake. Finally, we attempt to reconcile apparent differences between loss totals for two databases tracking similar information

Science and Technology Issues in the 115th Congress

Science and technology (S&T) have a pervasive influence over a wide range of issues confronting the nation. Public and private research and development spur scientific and technological advancement. Such advances can drive economic growth, help address national priorities, and improve health and quality of life. The constantly changing nature and ubiquity of science and technology frequently create public policy issues of congressional interest. The federal government supports scientific and technological advancement directly by funding and performing research and development and indirectly by creating and maintaining policies that encourage private sector efforts. Additionally, the federal government establishes and enforces regulatory frameworks governing many aspects of S&T activities. This report briefly outlines an array of science and technology policy issues that may come before the 115th Congress. Given the rapid pace of S&T advancement and its importance in many diverse public policy issues, S&T-related issues not discussed in this report may come before the 115th Congress. The selected issues are grouped into 9 categories: - Overarching S&T Policy Issues, - Agriculture, - Biomedical Research and Development, - Defense, - Energy, - Environment and Natural Resources, - Homeland Security, - Information Technology, - Physical and Material Sciences, and - Space. Each of these categories includes concise analysis of multiple policy issues. The material presented in this report should be viewed as illustrative rather than comprehensive. Each section identifies CRS reports, when available, and the appropriate CRS experts to contact for further information and analysis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis