When genetic load does not correlate with phenotypic spectrum: lessons from the GnRH receptor (GNRHR).

CONTEXT: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. OBJECTIVE: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. SUBJECTS: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. RESULTS: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. CONCLUSIONS: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes.

Iowa Smart Planning Task Force Report

In the 2010 legislative session, the General Assembly passed and the Governor signed into law Senate File 2389 (SF 2389), which provided guidance for Smart Planning in Iowa and established the Iowa Smart Planning Task Force. This Task Force was charged with recommending policies and strategies for creating a stronger planning culture in Iowa, producing more resilient and sustainable communities. The Task Force, along with its two committees and four workgroups, met throughout the summer and fall of 2010 to identify and review best practices, consult local and national experts, and craft recommendations in the best interest of Iowans. A public input process was also implemented, resulting in improved recommendations.

The use of 3D planning in facial surgery: Preliminary observations.

Three-dimensional (3D) planning is becoming a more commonly used tool in maxillofacial surgery. At first used only virtually, 3D planning now also enables the creation of useful intraoperative aids such as cutting guides, which decrease the operative difficulty. In our center, we have used 3D planning in various domains of facial surgery and have investigated the advantages of this technique. We have also addressed the difficulties associated with its use. 3D planning increases the accuracy of reconstructive surgery, decreases operating time, whilst maintaining excellent esthetic results. However, its use is restricted to osseous reconstruction at this stage and once planning has been undertaken, it cannot be reversed or altered intraoperatively. Despite the attractive nature of this new tool, its uses and practicalities must be further evaluated. In particular, cost-effectiveness, hospital stay, and patient perceived benefits must be assessed.

Supplemental Information to the August 2008 Long Term Recovery Planning Task Force Report, August 2008

Eighty-five of 99 Iowa counties were declared Presidential Disaster Areas for Public Assistance and/orIndividual Assistance as a result of the tornadoes, storms, and floods over the incident period May 25 through August 13, 2008. Response dominated the state’s attention for weeks, with a transition to recovery as the local situations warranted. The widespread damage and severity of the impact on Iowans and their communities required a statewide effort to continue moving forward despite being surrounded by adversity. By all accounts, it will require years for the state to recover from these disasters. With an eye toward the future, recovery is underway across Iowa. As part of the Rebuild Iowa efforts, the Long Term Recovery Planning Task Force was charged with responsibilities somewhat different from other topical Task Force assignments. Rather than assess damage and report on how the state might address immediate needs, the Long Term Recovery Planning Task Force is directed to discuss and discern the best approach to the lengthy recovery process. Certainly, the Governor and Lieutenant Governor expect the task to be difficult; when planning around so many critical issues and overwhelming needs, it is challenging to think to the future, rather than to rise to the current day’s needs.

Soil compaction and eucalyptus growth in response to forwarder traffic intensity and load

During timber exploitation in forest stands harvesting machines pass repeatedly along the same track and can cause soil compaction, which leads to soil erosion and restricted tree root growth. The level of soil compaction depends on the number of passes and weight of the wood load. This paper aimed to evaluate soil compaction and eucalyptus growth as affected by the number of passes and wood load of a forwarder. The study was carried out in Santa Maria de Itabira county, Minas Gerais State - Brazil, on a seven-year-old eucalyptus stand planted on an Oxisol. The trees were felled by chainsaw and manually removed. Plots of 144 m² (four rows 12 m long in a 3 x 2 m spacing) were then marked off for the conduction of two trials. The first tested the traffic intensity of a forwarder which weighed 11,900 kg and carried 12 m³ wood (density of 480 kg m-3) and passed 2, 4, and 8 times along the same track. In the second trial, the forwarder carried loads of 4, 8, and 12 m³ of wood, and the machine was driven four times along the same track. In each plot, the passes affected four rows. Eucalyptus was planted in 30 x 30 x 30 cm holes on the compacted tracks. The soil in the area is clayey (470 clay and 440 g kg-1 sand content) and at depths of 0-5 cm and 5-10 cm, respectively, soil organic carbon was 406 and 272 g kg-1 and the moisture content during the trial 248 and 249 g kg-1. These layers were assessed for soil bulk density and water-stable aggregates. The infiltration rate was measured by a cylinder infiltrometer. After 441 days the measurements were repeated, with additional analyses of: soil organic carbon, total nitrogen, N-NH4+, N-NO3-, porosity, and penetration resistance. Tree height, stem diameter, and stem dry matter were measured. Forwarder traffic increased soil compaction, resistance to penetration and microporosity while it reduced the geometric mean diameter, total porosity, macroporosity and infiltration rate. Stem dry matter yield and tree height were not affected by soil compaction. Two passes of the forwarder were enough to cause the disturbances at the highest levels. The compaction effects were still persistent 441 days after forwarder traffic.

Iowa Trails: Connecting People and Trails: Local Community Planning for Bicyclists and Pedestrians, 2000

Many communities in Iowa have expressed a desire to develop a plan for better accommodating pedestrians and bicyclists in their community. This desire results from the recognition that walking and bicycling are popular recreational activities and, are increasingly important as “alternative transportation modes.” Recognizing the desire on the part of communities to create better conditions for bicycling and walking, the Iowa DOT developed this handbook as part of Iowa Trails 2000. This handbook outlines the steps and resources required to create a comprehensive system of bicycle and pedestrian facilities. Such a system can serve local needs and connect communities to the Iowa State Trails System and other regional attractions.

Smart Planning in Iowa - A Guide to Principles, Strategies and Policy Tools

This guide was created to aid communities in the process of smart planning and is organized around the 10 Smart Planning Principles signed into Iowa law in 2010. A general description of the concept, strategies for encouraging use, policy tools for implementation, and a current Iowa example are presented for each Principle. In addition, a brief list of resources is provided to help local governments, community organizations and citizen planners find information and ideas on community involvement and incorporation of smart planning concepts in every day decisions.

Access by Capacity and Peak-Load Pricing

Several European telecommunications regulatory agencies have recently introduced a fixed capacity charge (flat rate) to regulate access to the incumbent's network. The purpose of this paper is to show that the optimal capacity charge and the optimal access-minute charge analysed by Armstrong, Doyle, and Vickers (1996) have a similar structure and imply the same payment for the entrant. I extend the analysis tothe case where there is a competitor with market power. In this case, the optimalcapacity charge should be modified to avoid that the entrant cream-skims the market,fixing a longer or a shorter peak period than the optimal. Finally, I consider a multiproduct setting, where the effect of the product differentiation is exacerbated.

A Transportation Safety Planning Tool for the City of Ames, August 2011

The historically-reactive approach to identifying safety problems and mitigating them involves selecting black spots or hot spots by ranking locations based on crash frequency and severity. The approach focuses mainly on the corridor level without taking the exposure rate (vehicle miles traveled) and socio-demographics information of the study area, which are very important in the transportation planning process, into consideration. A larger study analysis unit at the Transportation Analysis Zone (TAZ) level or the network planning level should be used to address the needs of development of the community in the future and incorporate safety into the long-range transportation planning process. In this study, existing planning tools (such as the PLANSAFE models presented in NCHRP Report 546) were evaluated for forecasting safety in small and medium-sized communities, particularly as related to changes in socio-demographics characteristics, traffic demand, road network, and countermeasures. The research also evaluated the applicability of the Empirical Bayes (EB) method to network-level analysis. In addition, application of the United States Road Assessment Program (usRAP) protocols at the local urban road network level was investigated. This research evaluated the applicability of these three methods for the City of Ames, Iowa. The outcome of this research is a systematic process and framework for considering road safety issues explicitly in the small and medium-sized community transportation planning process and for quantifying the safety impacts of new developments and policy programs. More specifically, quantitative safety may be incorporated into the planning process, through effective visualization and increased awareness of safety issues (usRAP), the identification of high-risk locations with potential for improvement, (usRAP maps and EB), countermeasures for high-risk locations (EB before and after study and PLANSAFE), and socio-economic and demographic induced changes at the planning-level (PLANSAFE).

Different PTH response to oral peptone load and oral calcium load in patients with normocalcemic primary hyperparathyroidism, primary hyperparathyroidism, and healthy subjects.

BACKGROUND: Normocalcemic primary hyperparathyroidism (PHPT-N) is a condition that may have similar long-term implications to primary hyperparathyroidism (PHPT); however, differential diagnosis and treatment for parathyroid disorders are not clearly defined. We investigated the effect of an oral peptone and an oral calcium load on calcium-regulating hormones in PHPT-N compared with PHPT and healthy controls to provide a new potential diagnostic tool. DESIGN: Case-control study. METHODS: We evaluated serum gastrin, PTH, ionized calcium, and phosphate responses to oral calcium (1 g) and peptone (10 g) load in 22 PHPT and 20 PHPT-N patients matched for PTH serum values. Moreover, 30 healthy subjects were enrolled as controls. In 12 patients for each group, we also performed the oral peptone test adding aluminum hydroxide (AH) to suppress phosphate absorption. RESULTS: In PHPT patients, PTH increased significantly 30 min after the oral peptone load, while no significant increase was found in PHPT-N and controls. After oral calcium load, PTH remained stable in PHPT while it decreased dramatically in PHPT-N patients, and ionized calcium increased significantly in each of the three groups. Peptones plus AH induced a blunted PTH increase in the three groups. CONCLUSIONS: Considering the marked difference in PTH response elicited by peptones in PHPT compared with PHPT-N, we suggest that the oral peptone test could be added to the diagnostic evaluation of PHPT patients. In case of absent response to peptones, patients should have their serum calcium levels assessed twice a year in accordance with recent guidelines.

2009 Iowa’s Rail System Background Prepared by the Office of Systems Planning December 2010

Iowa’s Rail Environment Iowa’s rail transportation system provides both freight and passenger service. Rail serves a variety of trips, including those within Iowa and those to other states as well as to foreign markets. While rail competes with other modes, it also cooperates with those modes to provide intermodal services to Iowans. In 2009 Iowa’s rail transportation system could be described as follows: Freight Iowa’s 130,000-mile freight transportation system includes an extensive railroad network, a well-developed highway system, two bordering navigable waterways, and a pipeline network as well as air cargo facilities. While rail accounts for only 3 percent of the freight network, it carries 43 percent of Iowa’s freight tonnage. A great variety of commodities ranging from fresh fish to textiles to optical products are moved by rail. However, most of the Iowa rail shipments consist of bulk commodities, including grain, grain products, coal, ethanol, and fertilizers. The railroad network performs an important role in moving bulk commodities produced and consumed in the state to local processors, livestock feeders, river terminals and ports for foreign export. The railroad’s ability to haul large volumes, long distances at low costs will continue to be a major factor in moving freight and improving the economy of Iowa. Key 2008 Facts • 3,945 miles of track • 18 railroads • 49.5 million tons shipped • 39.7 million tons received • 2 Amtrak routes • 6 Amtrak stations • 66,286 rail passenger rides Key Rail Trends • slightly fewer miles being operated; • railroads serving Iowa has remained the same; • more rail freight traffic; • more tons hauled per car; • higher average rail rates per ton-mile since 2002; • more car and tons hauled per locomotive; and • more ton miles per gallon of fuel consumed. Iowa’s rail system and service has been evolving over time relative to its size, financial conditions, and competition from other modes.

Joint evolution of dispersal and inbreeding load.

Inbreeding avoidance is often invoked to explain observed patterns of dispersal, and theoretical models indeed point to a possibly important role. However, while inbreeding load is usually assumed constant in these models, it is actually bound to vary dynamically under the combined influences of mutation, drift, and selection and thus to evolve jointly with dispersal. Here we report the results of individual-based stochastic simulations allowing such a joint evolution. We show that strongly deleterious mutations should play no significant role, owing to the low genomic mutation rate for such mutations. Mildly deleterious mutations, by contrast, may create enough heterosis to affect the evolution of dispersal as an inbreeding-avoidance mechanism, but only provided that they are also strongly recessive. If slightly recessive, they will spread among demes and accumulate at the metapopulation level, thus contributing to mutational load, but not to heterosis. The resulting loss of viability may then combine with demographic stochasticity to promote population fluctuations, which foster indirect incentives for dispersal. Our simulations suggest that, under biologically realistic parameter values, deleterious mutations have a limited impact on the evolution of dispersal, which on average exceeds by only one-third the values expected from kin-competition avoidance.