Trilateral retinoblastoma: neuroimaging characteristics and value of routine brain screening on admission.

Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29-100 %) compared to 11 % (95 % CI 0-32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage.

Multiplan Spreadsheets for Highway and Hydraulic Engineering Computations in County Engineering Offices, HR-284, 1987

Multiplan spreadsheet solutions were developed for a set of hydraulic and highway engineering computations of common interest to county engineers. These include earthwork, vertical and horizontal curves, staking superelevated curves and sign inventories for highways. The hydraulic applications were ditch flow, runoff, culvert size and stage discharge.

Recruiting and Retaining Women and Minorities in Public Sector Engineering Positions, HR-348, 1995

The objective of phase one of this research was to assess the degree to which currently employed Iowa Department of Transportation (DOT) employees would be affected by a more aggressive policy to recruit and retain women and minority engineers. The DOT's "Future Agenda" was used as a baseline to focus on efforts to update and implement a recruitment plan that would target underrepresented classes. The primary question that emerged out of phase one was how could the Iowa DOT strengthen its ties with Iowa State University (ISU) to produce increased numbers of in-state applicants for engineering positions. This introduced the objective of phase two, which was to identify problem areas resulting in unacceptably high attrition rates for women, minorities, and to a lesser degree, Caucasian men in the College of Engineering at ISU, particularly Civil and Construction Engineering (CCE). Past research has focused on (1) projected shortages of qualified civil engineers, (2) the obstacles confronting women in a traditionally male-oriented profession, and (3) minorities who are often unprepared to succeed in the rigors of an engineering curriculum because of a lack of academic preparedness. The researchers in this study, in contrast, chose to emphasize institutional reasons why women, minorities, and some Caucasian men often feel a sense of isolation in the engineering program. It was found that one of the key obstacles to student retention is the lack of visibility of the civil engineering profession. The visibility problem led to the hypothesis that many engineering students do not have a clear conception of what the practice of civil engineering entails. It was found that this may be a better predictor of attrition than the stereotypical assumption that a majority of students leave their engineering programs because they are not academically able to compete. Recommendations are offered to strengthen the ties between ISU's Department of CCE and the Iowa DOT in order to counter the visibility issue. It was concluded that this is a vital step because over the next 5-15 years 40% of DOT engineers currently employed will be phasing into retirement. If the DOT expects to draw sufficient numbers of engineers from within the state of Iowa and if increasing numbers of them are to be women and minorities, a university connection will help to produce the qualified applicants to fulfill this need.

Engineering Study Automating Iowa's Speed Monitoring Program, HR-228, 1983

Excessive speed on State and County highways is recognized as a serious problem by many Iowans. Speed increases both the risk and severity of accidents. Studies conducted by the FHWA and NHTSA have concluded that if average speeds were increased by five MPH, fatalities would increase by at least 2,200 annually. Along with the safety problems associated with excessive speed are important energy considerations. When the national speed limit was lowered to 55 MPH in 1974, a tremendous savings in fuel was realized. The estimated actual savings for automobiles amounted to 2.2 billion gallons, an average of 20.75 gallons for each of the 106 million automobiles registered in 1975. These benefits prompted the Federal-Aid Amendment of 1974 requiring annual State enforcement certification as a prerequisite for approval of Federal-aid highway projects. In 1978, the United States D.O.T. recommended to Congress significant changes in speed limit legislation designed to increase compliance with the national speed limit. The Highway Safety Act of 1978 provides for both withholding Federal-aid highway funds and awarding incentive grants based on speed compliance data submitted annually. The objective of this study was to develop and make operational, an automatic speed monitoring system which would have flexible capabilities of collecting accurate speed data on all road systems in Iowa. It was concluded that the Automatic Speed Monitoring Program in Iowa has been successful and needed data is being collected in the most economical manner possible.

Guidelines for County Engineering Decisions, HR-369, 1997

There has been a great deal of concern by county engineers and supervisors over constrained budgets, lack of resources and a deteriorating infrastructure, as they affect the secondary road system in Iowa. In addition, public input and/or political pressure have been increasing over the years. This study was initiated to determine the most important issues facing counties and document the way in which various Iowa counties have been addressing those issues. The list of issues was developed through meetings of county engineers and supervisors in each of the Iowa Department of Transportation (DOT) regions around the state. Questionnaires were sent to all engineers and supervisors statewide asking them how the various issues (e.g. snow and ice removal policies, Level "B" roads, and so on) were handled in their respective counties. The responses were then compiled into this document. The subjects selected and used include: county policies, ordinances, resolutions; snow and ice removal policy; dust control; Level "B" roads; vacating roads; rural development; private entrance construction and maintenance; roadside management practices; right of way encroachments and easements; personnel matters, staff and organization; communicating information to citizens; supervisor/ engineer relations; and county leasing/purchasing practices.

Soft Photogrammetry for Highway Engineering, HR-387, 1998

The SoftPlotter, a soft photogrammetric software and Silicon Graphics workstation, was used to evaluate the accuracy of soft photogrammetry and identify applications of this technology to highway engineering. A comparative study showed that SoftPlotter compares well with other software such as Socket and Integraph. The PC software TNTMips is inexpensive but needs further development to be comparable to SoftPlotter. The Campus Project showed that soft photogrammetry is accurate for traditional photogrammetric applications. It is also accurate for producing orthophoto and base maps for Geographic Information Systems (GISs). The Highway Project showed that soft photogrammetry is accurate for highway engineering and that the technical staff at the Iowa Department of Transportation (IA DOT) can be easily trained in this new technology. The research demonstrated that soft photogrammetry can be used with low-flight helicopter photography for large-scale mapping in highway engineering. The researchers recommend that research be conducted to test the use of digital cameras instead of the traditional aerial cameras in helicopter photography. Research that examines the use of soft photogrammetry with video logging imagery for inventory and GIS studies in highway maintenance is also recommended. Research is also warranted into the integration of soft photogrammetry with virtual reality, which can be used in three-dimensional designing and visualization of highways and subdivisions in real time. The IA DOT owns one analytical plotter and two analogue plotters. The analytical plotter is used for aerial triangulation, and the analogue plotters are used for plotting. However, neither is capable of producing orthophotos. Therefore, the researchers recommend that the IA DOT purchase soft photogrammetric workstations for orthophoto production, and if and when required, use it for aerial triangulation and plotting. In the future, the analogue plotters may become obsolete. At that time, the researchers recommend that the analogue plotters be phased out and replaced by soft photogrammetric workstations.

Engineering Study for the Evaluation of Public Road Administration and Maintenance Alternatives, HR-265, 1985

Iowa's public road system of 112,000 miles is one of the largest and the best in the nation. It represents a considerable financial investment of taxpayer revenues over the years. And, it requires a sustained investment to preserve an economical level of transport service into the future. In 1982, a Governor's Blue Ribbon Transportation Task Force evaluated the effectiveness of Iowa's entire transportation system. Four important Task Force recommendations dealt with public road administrative issues in Iowa. These issues were related to: (1) Design criteria and levels of maintenance; (2) Consistency in the use of standards among jurisdictions; (3) Consolidation of maintenance operations at one jurisdiction level; and (4) Jurisdicational authority for roads; The issues formed the background for Research Project HR-265.

High b-value Diffusion-weighted Imaging: A Sensitive Method to Reveal White Matter Changes in Schizophrenia

Background: b-value is the parameter characterizing the intensity of the diffusion weighting during image acquisition. Data acquisition is usually performed with low b value (b~1000 s/mm2). Evidence shows that high b-values (b>2000 s/mm2) are more sensitive to the slow diffusion compartment (SDC) and maybe more sensitive in detecting white matter (WM) anomalies in schizophrenia.Methods: 12 male patients with schizophrenia (mean age 35 +/-3 years) and 16 healthy male controls matched for age were scanned with a low b-value (1000 s/mm2) and a high b-value (4000 s/mm2) protocol. Apparent diffusion coefficient (ADC) is a measure of the average diffusion distance of water molecules per time unit (mm2/s). ADC maps were generated for all individuals. 8 region of interests (frontal and parietal region bilaterally, centrum semi-ovale bilaterally and anterior and posterior corpus callosum) were manually traced blind to diagnosis.Results: ADC measures acquired with high b-value imaging were more sensitive in detecting differences between schizophrenia patients and healthy controls than low b-value imaging with a gain in significance by a factor of 20- 100 times despite the lower image Signal-to-noise ratio (SNR). Increased ADC was identified in patient's WM (p=0.00015) with major contributions from left and right centrum semi-ovale and to a lesser extent right parietal region.Conclusions: Our results may be related to the sensitivity of high b-value imaging to the SDC believed to reflect mainly the intra-axonal and myelin bound water pool. High b-value imaging might be more sensitive and specific to WM anomalies in schizophrenia than low b-value imaging

CHO cell engineering to prevent polypeptide aggregation and improve therapeutic protein secretion.

The ability to efficiently produce recombinant proteins in a secreted form is highly desirable and cultured mammalian cells such as CHO cells have become the preferred host as they secrete proteins with human-like post-translational modifications. However, attempts to express high levels of particular proteins in CHO cells may consistently result in low yields, even for non-engineered proteins such as immunoglobulins. In this study, we identified the responsible faulty step at the stage of translational arrest, translocation and early processing for such a "difficult-to-express" immunoglobulin, resulting in improper cleavage of the light chain and its precipitation in an insoluble cellular fraction unable to contribute to immunoglobulin assembly. We further show that proper processing and secretion were restored by over-expressing human signal receptor protein SRP14 and other components of the secretion pathway. This allowed the expression of the difficult-to-express protein to high yields, and it also increased the production of an easy-to-express protein. Our results demonstrate that components of the secretory and processing pathways can be limiting, and that engineering of the secretory pathway may be used to improve the secretion efficiency of therapeutic proteins from CHO cells.

Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide.

PURPOSE: In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy. EXPERIMENTAL DESIGN: The methylation status of MGMT in the tumor biopsies was evaluated in 38 patients undergoing resection for newly diagnosed glioblastoma and enrolled in a Phase II trial testing concomitant and adjuvant temozolomide and radiation. The epigenetic silencing of the MGMT gene was determined using methylation-specific PCR. RESULTS: Inactivation of the MGMT gene by promoter methylation was associated with longer survival (P = 0.0051; Log-rank test). At 18 months, survival was 62% (16 of 26) for patients testing positive for a methylated MGMT promoter but reached only 8% (1 of 12) in absence of methylation (P = 0.002; Fisher's exact test). In the presence of other clinically relevant factors, methylation of the MGMT promoter remains the only significant predictor (P = 0.017; Cox regression). CONCLUSIONS: This prospective clinical trial identifies MGMT-methylation status as an independent predictor for glioblastoma patients treated with a methylating agent. The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.

Creating a list of low-value health care activities in Swiss primary care.

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.

Predictive value of readiness, importance, and confidence in ability to change drinking and smoking.

BACKGROUND: Visual analog scales (VAS) are sometimes used to assess change constructs that are often considered critical for change. Aims of Study: 1.) To determine the association of readiness to change, importance of changing and confidence in ability to change alcohol and tobacco use at baseline with the risk for drinking (more than 21 drinks per week/6 drinks or more on a single occasion more than once per month) and smoking (one or more cigarettes per day) six months later. 2.) To determine the association of readiness, importance and confidence with alcohol (number of drinks/week, number of binge drinking episodes/month) and tobacco (number of cigarettes/day) use at six months. METHODS: This is a secondary analysis of data from a multi-substance brief intervention randomized trial. A sample of 461 Swiss young men was analyzed as a prospective cohort. Participants were assessed at baseline and six months later on alcohol and tobacco use, and at baseline on readiness to change, importance of changing and confidence in ability to change constructs, using visual analog scales ranging from 1-10 for drinking and smoking behaviors. Regression models controlling for receipt of brief intervention were employed for each change construct. The lowest level (1-4) of each scale was the reference group that was compared to the medium (5-7) and high (8-10) levels. RESULTS: Among the 377 subjects reporting unhealthy alcohol use at baseline, mean (SD) readiness, importance and confidence to change drinking scores were 3.9 (3.0), 2.7 (2.2) and 7.2 (3.0), respectively. At follow-up, 108 (29%) reported no unhealthy alcohol use. Readiness was not associated with being risk-free at follow-up, but high importance (OR 2.94; 1.15, 7.50) and high confidence (OR 2.88; 1.46, 5.68) were. Among the 255 smokers at baseline, mean readiness, importance and confidence to change smoking scores were 4.6 (2.6), 5.3 (2.6) and 5.9 (2.7), respectively. At follow-up, 13% (33) reported no longer smoking. Neither readiness nor importance was associated with being a non-smoker, whereas high confidence (OR 3.29; 1.12, 9.62) was. CONCLUSIONS: High confidence in ability to change was associated with favorable outcomes for both drinking and smoking, whereas high importance was associated only with a favorable drinking outcome. This study points to the value of confidence as an important predictor of successful change for both drinking and smoking, and shows the value of importance in predicting successful changes in alcohol use. TRIAL REGISTRATION NUMBER: ISRCTN78822107.