Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by interleukin (IL)-1b. Canakinumab inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 wk double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150mg divided in doses every 4 wks (50þ50þ25þ25mg [q4wk]) or colchicine 0.5mg p.o. daily for 16 wks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to number of flares occurring during first 16 wks. Secondary outcomes included number of patients with flares and C-reactive protein (CRP) levels during the first 16 wks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine couldn't be determined. Based on a negative binomialmodel, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25mg 0.60, 50mg 0.34, 100mg 0.28, 200mg 0.37, 300mg 0.29, q4wk 0.38; p_0.05). Percentage of patients with flares was lower for all canakinumab groups (25mg 27.3%, 50mg 16.7%, 100mg 14.8%, 200mg 18.5%, 300mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p_0.05 for all). Median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN¼3 mg/L) throughout the 16 wk period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg), 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. 1 fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusions: In this randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine and was well tolerated.Disclosure statement: U.A., A.B., G.K., D.R. and P.S. are employees of and have stock options or bold holdings with Novartis Pharma AG. E.M. is a principal investigator for Novartis Pharmaceuticals Corporation. E.N. has received consulting fees from Roche. N.S. has received research grants from Novartis Pharmaceuticals Corporation. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Pediatric patient classification system: improvement of an instrument

Objective Improve the content validity of the instrument for classification of pediatric patients and evaluate its construct validity. Method A descriptive exploratory study in the measurement of the content validity index, and correlational design for construct validation through exploratory factor analysis. Results The content validity index for indicators was 0.99 and it was 0.97 for graded situations. Three domains were extracted in the construct validation, namely: patient, family and therapeutic procedures, with 74.97% of explained variance. The instrument showed evidences of content and construct validity. Conclusion The validation of the instrument occurred under the approach of family-centered care, and allowed incorporating some essential needs of childhood such as playing, interaction and affection in the content of the instrument.


Watershed Improvement Review Board Calendar Year 2006 Annual Report, January 31, 2007

The Iowa Watershed Improvement Review Board (WIRB) was created by the Iowa Legislature and signed into law by the Governor in 2005 as Senate File 200. This statute is now codified in Iowa Code Chapter 466A. The fifteen-member Board conducted eight meetings throughout the year in-person or via teleconference. Meetings were held January 24, February 27, March 13, May 15, August 7, September 20, October 6, and December 18. Attachment 3 lists the board members and their organization affiliation. The Board appointed a five-member subcommittee to review and revise the Request For Applications (RFA) documents and submit recommendations to the full Board. The RFA documents were approved as modified at the May 15, 2006 Board meeting.

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2006

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2006

Improvement of the specificity of cancer detection by autofluorescence imaging in the tracheo-bronchial tree using backscattered violet light.

BACKGROUND: Autofluorescence bronchoscopy (AFB) is a highly sensitive tool for the detection of early bronchial cancers. However, its specificity remains limited due to primarily false positive results induced by hyperplasia, metaplasia and inflammation. We have investigated the potential of blue-violet backscattered light to eliminate false positive results during AFB in a clinical pilot study. METHODS: The diagnostic autofluorescence endoscopy (DAFE) system was equipped with a variable band pass filter in the imaging detection path. The backscattering properties of normal and abnormal bronchial mucosae were assessed by computing the contrast between the two tissue types for blue-violet wavelengths ranging between 410 and 490 nm in 12 patients undergoing routine DAFE examination. In a second study including 6 patients we used a variable long pass (LP) filter to determine the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system. RESULTS: (Pre-)neoplastic mucosa showed a clear wavelength dependence of the backscattering properties of blue-violet light while the reflectivity of normal, metaplastic and hyperplastic autofluorescence positive mucosa was wavelength independent. CONCLUSIONS: Our results showed that the detection of blue-violet light has the potential to reduce the number of false positive results in AFB. In addition we determined the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system.

Fiscal Year 2008-2012 Iowa Transportation Improvement Program

This document was prepared by the Iowa Department of Transportation to inform Iowans of planned investments in the state's transportation system over the next five years.

Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.

Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.

Improvement of a test-chamber for behavioral studies on adult females of Aedes aegypti (Linnaeus) (Diptera, Culicidae)

A test-chamber (K&L-Chamber) made of cardboard and acrylic plastic, and consisting in four sections (A, B, C and D) was developed by Klowden & Lea (1978) for Aedes aegypti host-seeking behavior studies. Later, Foster & Lutes (1985) also used an identical chamber to successfully evaluate the efficacy of electronic repellers. It was described here a modified K&L-Chamber for behavioral studies of Ae. aegypti adults. The chamber was made in polystyrene, consisting of three sections (A, B and C) and using a human hand and a fluorescent lamp as stimulus to attract the mosquitoes. The suitability of the present test-chamber was validated assaying 80 replicates and releasing 10 Ae. aegypti females in each replicate. The females were released in the section A and allowed to fly to the section C. A mean of 96.0% (s.e. 0.213) Ae. aegypti females successfully reached section C. The present test-chamber is cheaper and easier to handle and as efficient as K&L-Chamber, when compared to Foster & Lutes (1978) that noticed 93.8% of Ae. aegypti reaching the trap section.

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2007

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2007

2009-2013 Iowa Transportation Improvement Program

The Iowa Transportation Improvement Program (Program) is published to inform Iowans of planned investments in our state's transportation system. The Iowa Transportation Commission (Commission) and Iowa Department of Transportation (Iowa DOT) are committed to programming those investments in a fiscally responsible manner. Iowa's transportation system is multi-modal; therefore, the Program encompasses investments in aviation, transit, railroads, trails, and highways. A major component of the Program is the highway section. The FY2009-2013 highway section is financially balanced and was developed to achieve several objectives. The Commission's primary highway investment objective is the safety, maintenance and preservation of Iowa's existing highway system. The Commission has allocated an annual average of $321 million to achieve this objective. This includes $185 million in 2009 and $170 million annually in years 2010-2013 for preserving the interstate system. It includes $114 million in 2009, $100 million in 2010 and $90 million annually in years 2011-2013 for non-interstate pavement preservation. It includes $38 million annually in 2009 and 2010, and $35 million annually in years 2011-2013 for non-interstate bridges. In addition, $15 million annually is allocated for safety projects. However, due to increasing construction costs, flattened revenues and overall highway systems needs, the Commission acknowledges that insufficient funds are being invested in the maintenance and preservation of the existing highway system. Another objective involves investing in projects that have received funding from the federal transportation act and/or subsequent federal transportation appropriation acts. In particular, funding is being used where it will complete a project, corridor or useable segment of a larger project. As an investment goal, the Commission also wishes to advance highway projects that address the state's highway capacity and economic development needs. Projects that address these needs and were included for completion in the previous program have been advanced into this year's Program to maintain their scheduled completion. This program also includes a small number of other projects that generally either represent a final phase of a partially programmed project or an additional segment of a partially completed corridor. The TIME-21 bill, Senate File 2420, signed by Governor Chet Culver on April 22, provides additional funding to cities, counties and the Iowa DOT for road improvements. This will result in additional revenue to the Primary Road Fund beginning in the second half of FY2009 and gradually increase over time. The additional funding will be included in future highway programming objectives and proposals and is not reflected in this highway program. The Iowa DOT and Commission appreciate the public's involvement in the state's transportation planning process. Comments received personally, by letter, or through participation in the Commission's regular meetings or public input meetings held around the state each year are invaluable in providing guidance for the future of Iowa's transportation system. It should be noted that this document is a planning guide. It does not represent a binding commitment or obligation of the Commission or Iowa DOT, and is subject to change. You are invited to visit the Iowa DOT's Web site at iowadot.gov for additional and regular updates about the department's programs and activities.

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2008

Audit report on Mid-Iowa School Improvement Consortium, Carlisle, Iowa for the year ended June 30, 2008

2010- 2014 Iowa Transportation Improvement Program

The Iowa Transportation Improvement Program (Program) is published to inform Iowans of planned investments in our state’s transportation system. The Iowa Transportation Commission (Commission) and Iowa Department of Transportation (Iowa DOT) are committed to programming those investments in a fiscally responsible manner. A major component of the 2010-2014 Program is the full integration of funding allocated to the Iowa DOT from the American Recovery and Reinvestment Act of 2009 (Recovery Act). To date, the Recovery Act has provided over $400 million of additional federal funding for transportation in Iowa, including funding that is allocated to local governments and entities. Recovery Act funding will result in a record year for transportation construction in Iowa and the creation and retention of jobs. Opportunities for additionalRecovery Act transportation funding remain and will be pursued as they becomeavailable. While Recovery Act funding will make a one-time significant impact in addressing Iowa’s backlog of needs, it is important to note that there remains a large shortfall in sustained annual transportation investment to meet Iowa’s current and future critical transportation needs. In recognition of this shortfall, Governor Culver introduced and the legislature passed an I-JOBS proposal. I-JOBS will result in an additional $50 million of state funding to reduce structurally deficient and functionally obsolete bridges on the primary road system and approximately $10 million in funding for other modes of transportation including $3 million of new funding to support the expansion of passenger rail service in Iowa. I-JOBS, and the continuing gradual increase in funding due to TIME-21, will complement and extend the benefits of Recovery Act funding and set the stage for addressing the shortfall in annual funding in the next few years. Iowa’s transportation system is multi-modal; therefore, the Program encompasses investments in aviation, transit, railroads, trails, and highways. A major component of the Program is the highway section. The FY2010-2014 highway section is financially balanced and was developed to achieve several objectives. The Commission’s primary highway investment objective is stewardship (i.e. safety, maintenance and preservation) of Iowa’s existing highway system. The highway section includes an annual average of $104 million for preserving the interstate system; an annual average of $78 million for non-interstate pavement preservation; an annual average of $36 million for non-interstate bridges; and an annual average of $14 million for safety projects. Another objective is to maintain the scheduled completion of interstate and non-interstate capacity and economic development projects that were identified in the previous Program and this Program does so. The final Commission objective is to further address capacity and economic development needs and the Commission has done so by adding several such projects to the Program. Construction improvements are partially funded through the current federal transportation act, Safe, Accountable, Flexible, Efficient Transportation Equity Act: A Legacy for Users (SAFETEA-LU). The act will expire September 30, 2009. With the expiration of SAFETEA-LU, there is significant uncertainty in the forecast of federal revenues in the out-years of this Program. The Commission and Iowa DOT will monitor federal actions closely and make adjustments to the Program as necessary. The Iowa DOT and Commission appreciate the public’s involvement in the state’s transportation planning process. Comments received personally, by letter, or through participation in the Commission’s regular meetings or public input meetings held around the state each year are invaluable in providing guidance for the future of Iowa’s transportation system. It should be noted that this document is a planning guide. It does not represent a binding commitment or obligation of the Commission or Iowa DOT, and is subject to change. You are invited to visit the Iowa DOT’s Web site at iowadot.gov for additional and regular updates about the department’s programs and activities.

Statewide Transportation Improvement Program 2010-2013

Iowa’s Statewide Transportation Improvement Program (STIP) has been developed in conformance with the guidelines prescribed by 23 USC. The STIP is generated to provide the Federal Highway Administration (FHWA) and Federal Transit Administration (FTA) a listing of all projects that are candidates for federal aid from the FHWA and FTA for four federal fiscal years (FFY). Preceding the listings of federal-aid candidates are general comments concerning Iowa’s public participation process for selection of federal-aid projects and the basis for funding the proposed projects. Documents evidencing the Iowa Department of Transportation’s (Iowa DOT) authority to act concerning matters related to transportation, federal-aid expenditures and approvals of Metropolitan Planning Organizations’ (MPOs) Transportation Improvements Programs (TIPs) have been provided in past STIP’s and can be provided again upon request. The projects identified within the 2010-2013 STIP are divided into two groups. Projects proposed for funding from FHWA programs are shown first. FTA programs follow. Maps are included that identify locations of Iowa DOT District Planners, Metropolitan Planning Organizations (MPOs), Regional Planning affiliations (RPAs), and transit systems.

Brain dynamics underlying training-induced improvement in suppressing inappropriate action.

Inhibitory control, a core component of executive functions, refers to our ability to suppress intended or ongoing cognitive or motor processes. Mostly based on Go/NoGo paradigms, a considerable amount of literature reports that inhibitory control of responses to "NoGo" stimuli is mediated by top-down mechanisms manifesting ∼200 ms after stimulus onset within frontoparietal networks. However, whether inhibitory functions in humans can be trained and the supporting neurophysiological mechanisms remain unresolved. We addressed these issues by contrasting auditory evoked potentials (AEPs) to left-lateralized "Go" and right NoGo stimuli recorded at the beginning versus the end of 30 min of active auditory spatial Go/NoGo training, as well as during passive listening of the same stimuli before versus after the training session, generating two separate 2 × 2 within-subject designs. Training improved Go/NoGo proficiency. Response times to Go stimuli decreased. During active training, AEPs to NoGo, but not Go, stimuli modulated topographically with training 61-104 ms after stimulus onset, indicative of changes in the underlying brain network. Source estimations revealed that this modulation followed from decreased activity within left parietal cortices, which in turn predicted the extent of behavioral improvement. During passive listening, in contrast, effects were limited to topographic modulations of AEPs in response to Go stimuli over the 31-81 ms interval, mediated by decreased right anterior temporoparietal activity. We discuss our results in terms of the development of an automatic and bottom-up form of inhibitory control with training and a differential effect of Go/NoGo training during active executive control versus passive listening conditions.

Iowa Supreme Court Improvement Project for Child in Need of Assistance Cases: Annual Report and Proposed Policy Revisions.

The first part of a three year plan to evaluate and recommend improvements to Iowa's Juvenile Courts.