Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

2008 Affirmative Action in Iowa Annual Review

In with accordance 19B.5 of the Code of Iowa, this item has submitted the fiscal year 2008 Affirmative Action in Iowa report. The report details the progress we have made to balance our workforce in FY 2008. Just as importantly, the plan describes steps to put into practice our continued commitment to increasing diversity in the state’ workforce and details our response to the challenges we face as a result of increased talent competition. The State's renewed emphases on recruitments. along with greater oversight of state agency hiring practices, are key strategies that we must aggressively employ in competing for talent and balancing our workforce.

Iowa Budget Report Fiscal Year 2010.

Governor Chet Culver and Lt. Governor Patty Judge submitted their $6.2 billion budget for fiscal year 2010. The proposal recommends further budget cuts – rather than tax increases – to help meet the challenges of declining state revenues. “In recent months, we have reduced state government spending by nearly $180 million in order to maintain a balanced budget,” said Governor Culver. "My budget proposal for fiscal year 2010 will reflect a 6.5 percent cut to almost every state department and program,” the Governor continued. “In fact, 207 of the 253 line items in my budget proposal will be cut by 6.5 percent. That represents a savings of $400 million to Iowa taxpayers.”

Lending to the borrower from hell: Debt and default in the age of Philip II, 1556-1598

What sustained borrowing without third-party enforcement, in the early days of sovereignlending? Philip II of Spain accumulated towering debts while stopping all payments tohis lenders four times. How could the sovereign borrow much and default often? Weargue that bankers ability to cut off Philip II s access to smoothing services was key. Aform of syndicated lending created cohesion among his Genoese bankers. As a result,lending moratoria were sustained through a cheat the cheater mechanism (Kletzer andWright, 2000). Our paper thus lends empirical support to a recent literature emphasizingthe role of bankers incentives for continued sovereign borrowing.

On the concept of optimality interval

The approximants to regular continued fractions constitute `best approximations' to the numbers they converge to in two ways known as of the first and the second kind.This property of continued fractions provides a solution to Gosper's problem of the batting average: if the batting average of a baseball player is 0.334, what is the minimum number of times he has been at bat? In this paper, we tackle somehow the inverse question: given a rational number P/Q, what is the set of all numbers for which P/Q is a `best approximation' of one or the other kind? We prove that inboth cases these `Optimality Sets' are intervals and we give aprecise description of their endpoints.

Performance Report for Fiscal Year, 2005

I am pleased to present the performance report for the Iowa Department for the Blind for fiscal year 2005. This report is provided in compliance with sections 8E.210 and 216B.7 of the Code of Iowa. It contains valuable information about the services the Department and its partners provided for Iowans during the past fiscal year in the areas of vocational rehabilitation, library services, and resource management. Major accomplishments of the year included new food service opportunities in the Randolph-Sheppard program, extensive remodeling of the Adult Orientation and Adjustment Center, and continued national prominence in vocational rehabilitation as measured by the U.S. Rehabilitation Services Administration, which on June 13, 2005 released data on federal standards and indicators for the year ended September 30, 2004. Earnings ratios and the percentage of employment for vocational rehabilitation clients of the Department remain among the best in the nation. This is corroborated by a report released in September, 2005 by the U.S. Government Accountability Office, which tested and summarized datasets compiled by the U.S. Department of Education for the nation’s 80 vocational rehabilitation agencies. Overall, we met or exceeded 26 of 32 results targets included in this report. Key strategic challenges, developments, and trends are also discussed in the "Department Overview" that follows. Sincerely, Allen C. Harris Director, Iowa Department for the Blind

Performance Report for Fiscal Year, 2006

I am pleased to present the performance report for the Iowa Department for the Blind for fiscal year 2006. This report is provided in compliance with sections 8E.210 and 216B.7 of the Code of Iowa. It contains valuable information about the services the Department and its partners provided for Iowans during the past fiscal year in the areas of vocational rehabilitation, library services, and resource management. Major accomplishments of the year included successful administration of a federally-funded mentoring program (Pathfinders) that matches young adults ages 16-26 who are blind or visually impaired with mentors who also have vision loss, installed a state-of-the art digital recording studio in the library, and continued national prominence in vocational rehabilitation. Earnings ratios and the percentage of employment for vocational rehabilitation clients of the Department remain among the best in the nation, as measured by the U.S. Rehabilitation Services Administration, which on July 3, 2006 released data on federal standards and indicators for the year ended September 30, 2005. Overall, we met or exceeded 15 of 20 results targets included in this report. Key strategic challenges, developments, and trends are also discussed in the "Department Overview" that follows. Sincerely, Allen C. Harris Director, Iowa Department for the Blind

Performance Report for Fiscal Year, 2008

I am pleased to present the performance report for the Iowa Department for the Blind for fiscal year 2008. This report is provided in compliance with sections 8E.210 and 216B.7 of the Code of Iowa. It contains valuable information about results achieved because of the services that we and our partners provided to blind and visually impaired Iowans during the past fiscal year in the areas of Vocational Rehabilitation, Independent Living, Library Services, and Resource Management. We determine our competitive success in a number of ways. We look at the federal standards and indicators to learn our ranking in relation to the performance of other public rehabilitation agencies. We compare our library's production and circulation figures with those from previous years to determine trends. We set our own standards for success by looking at such factors as the number of successful case closures, average hourly wage at case closure, skills training provided, and compliance with regulations. Results show that the Department is working positively toward achieving its strategic goals of increasing the independence and productivity of blind Iowans and improving access to information for blind Iowans. Major accomplishments of the year included:  The selection of our Library as one of eight libraries to receive the new digital talking book machines and books in digital media from the National Library Service for the Blind and Physically Handicapped. Priority for distribution of the machines is given to Library patrons who are veterans.  The Department, the Iowa Braille School, and the Department of Education have been promoting the new expanded core curriculum as part of their continued efforts to improve the coordination and delivery of services to blind and visually impaired students in Iowa.  The Department's five-year grant funded Pathfinders mentoring program ended this year. A total of 49 blind youths aged 16-26 were paired with successful blind adult mentors. Assessments of the program clearly showed that participation in the program had a measurable positive effect on the youth involved.  Finally, earnings ratios and the percentage of employment for vocational rehabilitation clients of the Department are among the best in the nation, as measured by the U.S. Rehabilitation Services Administration's standards and indicators for the year ended September 30, 2007. Overall, we met or exceeded 13 of 18 targets included in this report. A discussion of the Department's services, customers, and organizational structure, and budget appears in the "Department Overview" that follows. Information pertaining to performance results appears in the final section of this document. The success of the Department's programs is evident in the success achieved by blind Iowans. It is reflected in the many blind persons who can be seen traveling about independently, going to their jobs and to the community and family activities in which they participate. Sincerely, Karen A. Keninger, Director Iowa Department for the Blind

Vertical Infrastructure Program Plan of Action, December 17, 2008

In order to promote the importance of our assets and to ensure continued and increasing funding for major maintenance and routine maintenance, in 2008 we intend to, annually update a list of facts relating to state buildings and the maintenance needs for those buildings. This information will support the case for increased and permanent funding

Charting Our Own Course: Today’s Challenges, Tomorrow’s Opportunities, December 2008

The Office of Energy Independence presents Iowa’s second annual energy independence plan, which highlights accomplishments achieved thus far and makes recommendations for the coming year. This plan shows that Iowa has made significant progress in building the foundation for reaching energy independence in just the past year. Continued investment and further efforts will enable Iowa to push toward even greater advances, while creating new jobs and diversifying local economies. With those aims in mind, the state has been investing extensively in the new energy economy. One important example is the Iowa Power Fund, an annual appropriation from the Iowa General Assembly administered by the Office of Energy Independence. In less than one year, the Office has received more than 160 project applications totaling more than $308 million in requests. The projects approved thus far will help advance Iowa’s wind and solar industries, foster new energy efficiency practices, and develop the bio fuels industry for a more economically and environmentally sustainable future. Iowa’s position as a leader in the new energy economy is dependent on the success of the Power Fund, and on the success of this plan. This plan clearly states that Iowa must boldly pursue a strong position in the emerging energy economy worldwide.

A randomized crossover study to compare efavirenz and etravirine treatment.

BACKGROUND: Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavourable blood lipid profile. We investigated the effect of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels. METHOD: Study participants did not complain of side-effects, had tolerated EFV for at least 3 months, with less than 50 copies/ml HIV-RNA. After randomization, the ETR-first group started with ETR (400 mg daily) [DOSAGE ERROR CORRECTED] with EFV-placebo and the EFV-first group with EFV with ETR-placebo. After 6 weeks, both groups switched to the alternate regimen. Nucleoside reverse transcriptase inhibitors were continued without any change. The primary end point was patient preference for the first or the second regimen, assessed after 12 weeks. RESULTS: Fifty-eight patients were enrolled with a median CD4 cell count of 589 cells/μl and the duration of previous EFV therapy was 3.9 years. Fifty-five patients completed the study. When asked about treatment preference after 12 weeks, 16 preferred EFV and 22 preferred ETR, whereas 17 did not express a preference (P = NS). Patients who continued EFV during the first phase of the trial preferred EFV (15/21, 71%), whereas patients who started with ETR were more likely to prefer ETR (n = 16/17, 94%). This order effect was strongly significant (P < 0.0001). Quality of sleep, depression, anxiety and stress scores did not differ significantly between groups. Median plasma cholesterol levels decreased by 0.7 mmol (29 mg/100 ml) after replacing EFV with ETR (P < 0.002). CONCLUSION: After substitution of EFV by ETR, patients did not express a significant preference for ETR. There was no measurable effect on neuropsychiatric symptoms and sleep. Cholesterol decreased.

Commission on the Status of Iowans of Asian & Pacific Islander Heritage (CAPI), Spring 2009

We are pleased to present the 2009 Spring Newsletter summarizing programs and achievements from this past year. Although many challenges lie ahead as this deepening financial crisis takes its toll, CAPI remains steadfast in its commitment to serve the needs of all Asian and Pacific Islanders of Iowa. Thank you for your continued support! We look forward to having another productive year!

Annual Report of the Iowa Grape and Wine Development Commission for Fiscal Year, 2008

FY2008 was a productive year for the Iowa Grape and Wine Development Commission. Sixteen proposals were recommended for funding from FY2008 funds and carryover totaling just over $396,000 in outlays. Included in the approved proposals were staffing and equipment for the Midwest Grape and Wine Industry Institute’s wine diagnostics laboratory at Iowa State University, continued support for the viticulturist position at Des Moines Area Community College, funding for the second annual Mid-American Wine Competition, and assistance for marketing and promotion of Ice coats an Iowa vineyard after a February 2008 ice storm. Photo by Mike White and courtesy of Iowa State University. 16 two wine trail associations and seven festivals and events. Commission funding supported a salaried position within IDALS to manage the Iowa Grape and Wine Development Fund and to serve as the Director of the Iowa Grape and Wine Development Commission. The Commission approved funding for a Scholarship Program. The formally created Scholarship Committee met twice in FY2008 to finalize details for the Program and to approve scholarships to twenty-six applicants to aid with the expenses of accredited coursework. Based on data collected by IDALS, the Iowa Department of Economic Development, the Iowa Alcoholic Beverages Division, and Iowa State University the Iowa grape and wine industry appears to continue to be very viable and growth continues at a strong pace. Presently, Iowa ranks 14th in the nation for the number of wineries, and wine produced in the state for 2008 was estimated at a market value in excess of $14.0 million. A tabulation of the budget revealed that just over $1,080,000 in wine gallonage tax appropriations and legislative appropriations have been deposited into the Grape and Wine Development Fund from FY2003 through FY2008. Removing encumbered funds, expenditures have totaled just over $942,500 during that same time. “Financial” funding – used for fostering public awareness and participation of industry events - increased from 6% of expenditures in FY2007 to 9% in FY2008. Used for support of research, education, and outreach, a little over 80% of expenditures and encumbered funds were earmarked for “Technical” spending. Over time, funds invested in “Technical” programs will translate into an increasingly educated and institutionally-supported industry. Local, regional, and statewide events also appeared to be increasing in popularity. The Commission was encouraged to see increased support for these events. It is hoped, too, that the Scholarship Program will provide needed funding to help meet the educational goals of the industry’s workforce. As they continue to support Iowa’s grape and wine industry, the Commissioners look forward to working with individuals, commercial enterprises, state and federal agencies, and industry-sponsored institutions in FY2009 and in years to come.

Six Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Results From the First Three Years of the FREEDOM Extension

Background/Purpose: Denosumab (DMAb) is an approved therapy for the treatment of postmenopausal women with osteoporosis at increased risk for fracture. A favorable risk/benefit profile was demonstrated in the pivotal, 3-year FREEDOM trial (Cummings et al NEJM 2009). The open-label, active-treatment FREEDOM Extension study is investigating the efficacy and safety of DMAb for up to 10 years. The Extension trial enrolled women who had received DMAb or placebo in FREEDOM and provides an opportunity to evaluate the long-term efficacy and safety of continuous DMAb treatment (long-term group), and to replicate the DMAb findings observed in FREEDOM (cross-over group). Here, we report the results from the first 3 years of the Extension, representing up to 6 continuous years of DMAb exposure. Methods: During the Extension, each woman is scheduled to receive 60 mg DMAb every 6 months and supplemental calcium and vitamin D daily. For the analyses reported here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years of exposure (long-term group) and women from the FREEDOM placebo group received 3 years of DMAb exposure (cross-over group). Results: Of the 5928 women eligible for the Extension, 4550 (77%) enrolled (N_2343 long-term; N_2207 cross-over). In the long-term group, further significant mean increases in bone mineral density (BMD) occurred 4044 for cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip (Figure). During the first 3 years of DMAb treatment during the Extension, the cross-over group had significant mean gains in BMD at the lumbar spine (9.4%) and total hip (4.8%), similar to those observed in the long-term DMAb group during the first 3 years of FREEDOM (lumbar spine, 10.1%; total hip, 5.7%). Serum CTX was rapidly and similarly reduced after the 1st (cross-over) or 7th (long-term) DMAb dose with the characteristic attenuation observed at the end of the dosing period. In the cross-over group, yearly incidences of new vertebral and nonvertebral fractures were lower than in the FREEDOM placebo group. Fracture incidence remained low in the long-term group. Incidences of adverse events (AEs) and serious AEs did not increase over time with DMAb treatment. There were 2 subjects with AEs adjudicated to ONJ in the cross-over group and 2 in the long-term group. Both cases in the cross-over group healed completely and without further complications; 1 of these subjects continues to receive DMAb. Both women in the long-term group continue to be followed. No atypical femur fractures have been observed to date. Figure. Percent changes in bone mineral density during FREEDOM and the Extension Conclusion: DMAb treatment for 6 continuous years (long-term group) remained well tolerated, maintained reduced bone turnover, and continued to significantly increase BMD. Fracture incidence remained low. DMAb treatment for 3 years in the cross-over group reproduced the original observations in FREEDOM

A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance.

We report the study of a large American family displaying autosomal dominant retinitis pigmentosa with reduced penetrance, a form of hereditary retinal degeneration. Although the inheritance pattern and previous linkage mapping pointed to the involvement of the PRPF31 gene, extensive screening of all its exons and their boundaries failed in the past to reveal any mutation. In this work, we sequenced the entire PRPF31 genomic region by both the classical Sanger method and ultrahigh throughput (UHT) sequencing. Among the many variants identified, a single-base substitution (c.1374+654C>G) located deep within intron 13 and inside a repetitive DNA element was common to all patients and obligate asymptomatic carriers. This change created a new splice donor site leading to the synthesis of two mutant PRPF31 isoforms, degraded by nonsense-mediated mRNA decay. As a consequence, amounts of PRPF31 mRNA derived from the mutant allele were very reduced, with no evidence of mutant proteins being synthesized. Our results indicate that c.1374+654C>G causes retinitis pigmentosa via haploinsufficiency, similar to the vast majority of PRPF31 mutations described so far. We discuss the potential of UHT sequencing technologies in mutation screening and the continued identification of pathogenic splicing mutations buried deep within intronic regions.