Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.

Senecio pterophorus DC., a new alien species in the European mainland

Senecio pterophorus DC. is an erect, semilignose shrub (fig. 1) which grows up to 2 m high. Is a chamaephyte basipetal branch-shedder (ORSHAN, Plant pheno-morphological studies in Mediterranean type ecosystems: 210-211. 1989) whose new branches appear below inflorescences but not from the lower parts of the plant. Leaves lanceolate. Stems are annual and develop at their apex a great number of small (up to 15 mm in diameter) yellow capitula which are grouped in a corymbose-paniculated inflorescence (HARVEY & SONDER, Flora Capensis: Cape Colony, Caffraria & Port Natal 3: 386.1865).

2me catalogue d'estampes composant le cabinet de M. L... [Laterrade] Vente 20 déc. 1858... / rédigé par A. Rochoux... ; [expert] Vignères

[Vente. Estampes. 1858-12-20 - 1858-12-22. Paris]

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

Bonded, Thin-Lift, Non-Reinforced Portland Cement Concrete Resurfacing, MLR-77-2, 1977

A research project involving 2, 3, 4, and 5 in. (5.1, 7.6, 10.2, and 12.7 cm) of bonded portland cement concrete (PCC) overlay on a 1.3 mile (2.1 km) PCC pavement was conducted in Clayton County, Iowa, during September 1977, centering on the following objectives: (1) Determine the mixing and proportioning procedures required in using a conventional, central mix proportioning plant to produce a dense PCC mixture using standard mixes with super water reducing admixtures; (2) Determine the economics, longevity and maintenance performance of a bonded, thin-lift, non-reinforced PCC resurfacing course using conventional procedures, equipment and concrete paving mixtures both with and without super water reducing admixtures; and (3) Determine if an adequate bond between the existing pavement and an overlay of thin-lift, dense, non-reinforced PCC can be obtained with only special surface cleaning and no surface removal or grinding. The conclusions are as follows: (1) Normal mixing equipment and proportioning procedures could be used using a conventional central-mix proportioning plant. This was successful when used with super water reducing admixtures. Only minor changes need be made in procedures and timing. (2) The time has been too short since the completion of the project to determine how the new pavement will perform, however, initially it appears that the method is economical and no reason is seen at this time why the life of the pavement should not be comparable to an all new pavement. (3) The initial test results show that bond strength, regardless of which method of cleaning is used, scarifying, sand blasting or water blasting, far exceed what is considered the minimum bond strength of 200 psi (1379 kPa) except where the paint stripes were intentionally left, thus showing that the paint must be removed. (4) It appears that either cement and water grout or sand, cement and water grout may be used and still obtain the required bond.

Value of positron emission tomography in full-thickness chest wall resections for malignancies.

Preoperative imaging for resection of chest wall malignancies is generally performed by computed tomography (CT). We evaluated the role of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in planning full-thickness chest wall resections for malignancies. We retrospectively included 18 consecutive patients operated from 2004 to 2006 at our institution. Tumor extent was measured by CT and PET, using the two largest perpendicular tumor extensions in the chest wall plane to compute the tumor surface assuming an elliptical shape. Imaging measurements were compared to histopathology assessment of tumor borders. CT assessment consistently overestimated the tumor size as compared to PET (+64% vs. +1%, P<0.001). Moreover, PET was significantly better than CT at defining the size of lesions >24 cm(2) corresponding to a mean diameter >5.5 cm or an ellipse of >4 cm x 7.6 cm (positive predictive value 80% vs. 44% and specificity 93% vs. 64%, respectively). Metabolic PET imaging was superior to CT for defining the extent of chest wall tumors, particularly for tumors with a diameter >5.5 cm. PET can complement CT in planning full-thickness chest wall resection for malignancies, but its true value remains to be determined in larger, prospective studies.

Freeze-Thaw Durability of Concretes with Infilling of Ettringite in Voids, Phase 2, MLR-94-9, 1997

Examination of field portland cement concrete cores, from Iowa pavements with premature deterioration, reveals extensive infilling of calcium sulfate aluminum (CSA) compound in their air voids. A previous study (Phase I) has shown some evidence of the correlation between freeze-thaw durability of concretes and ettringite infilling. To further verify the previous observation, a more extensive experimental program was conducted in this Phase 2 study. A total of 101 concrete mixes were examined. Seven cements, six fly ashes, two water reducers and three coarse aggregates were used in the concrete mixes. Specimens were under moist curing for up to 223 days before being subjected to the freeze-thaw cycling. An environmental treatment consisting of three consecutive wet [70 deg F (21 deg C) in distilled water]/dry [120 deg F (49 deg C) in oven] cycles was applied to some specimens. Immediately prior to the freeze-thaw cycling, most specimens were examined by a low-vacuum scanning electron microscope (SEM) for their microstructure. The results obtained further demonstrate the correlation between concrete freeze-thaw response and CSA compound infilling in the air voids. The extent of the infilling depends on the period of moist curing as well as the wet/dry treatment. The extent of the infilling also relates to materials used. Concrete mixes with extensive infilling are more vulnerable to the freeze-thaw attack. Based on the obtained results, material criteria on cements and fly ashes for mainline paving were proposed for minimizing potential infilling of CSA compound in concrete.

Quantifying Uncertainty in Real Time Performance Measurement for Highway Winter Maintenance Operations – Phase 2, RB03-013, 2014

Winter weather in Iowa is often unpredictable and can have an adverse impact on traffic flow. The Iowa Department of Transportation (Iowa DOT) attempts to lessen the impact of winter weather events on traffic speeds with various proactive maintenance operations. In order to assess the performance of these maintenance operations, it would be beneficial to develop a model for expected speed reduction based on weather variables and normal maintenance schedules. Such a model would allow the Iowa DOT to identify situations in which speed reductions were much greater than or less than would be expected for a given set of storm conditions, and make modifications to improve efficiency and effectiveness. The objective of this work was to predict speed changes relative to baseline speed under normal conditions, based on nominal maintenance schedules and winter weather covariates (snow type, temperature, and wind speed), as measured by roadside weather stations. This allows for an assessment of the impact of winter weather covariates on traffic speed changes, and estimation of the effect of regular maintenance passes. The researchers chose events from Adair County, Iowa and fit a linear model incorporating the covariates mentioned previously. A Bayesian analysis was conducted to estimate the values of the parameters of this model. Specifically, the analysis produces a distribution for the parameter value that represents the impact of maintenance on traffic speeds. The effect of maintenance is not a constant, but rather a value that the researchers have some uncertainty about and this distribution represents what they know about the effects of maintenance. Similarly, examinations of the distributions for the effects of winter weather covariates are possible. Plots of observed and expected traffic speed changes allow a visual assessment of the model fit. Future work involves expanding this model to incorporate many events at multiple locations. This would allow for assessment of the impact of winter weather maintenance across various situations, and eventually identify locations and times in which maintenance could be improved.

Grau de millora del compliment de l'exercici físic en pacients amb diabetus mellitus tipus 2

L’objectiu d’aquest projecte és conèixer quin mètode és el més efectiu per millorar el compliment de prescripció d’exercici físic, en persones que pateixen Diabetis Mellitus tipus 2. La Hipòtesi del treball, és que els pacients del grup intervenció tindran un grau de millora més elevat que els pacients del grup control. Per dur-lo a terme s’analitzarà el grau d’exercici físic de persones amb diabetis Mellitus, a través de la enquesta IPAQ. Es faran dos grups: Grup intervenció, que seran persones que participen en les sessions del Programa Pacient expert. Grup control, que seran persones que van a les visites de control amb la infermera del CAP. També s’utilitzarà una enquesta de dades demogràfiques per valorar el nivell d’estudis i la situació laboral dels participants. Aquest estudi es portarà a terme en 10 centres d’atenció primària del Bages, per professionals d’infermeria i durant 26 mesos. Com a limitacions de l’estudi trobem que el grup intervenció i el grup control no rebran el mateix tipus de formació i es portaran a terme en períodes de temps diferents, pot haver abandonament per part dels usuaris i pot ser que els infermers dels CAP on es portarà a terme arribin a conèixer l’estudi.

Development of In Situ Detection Methods for Materials-Related Distress (MRD) in Concrete Pavements: Phase 2, HR-1081, 2005

This project utilized information from ground penetrating radar (GPR) and visual inspection via the pavement profile scanner (PPS) in proof-of-concept trials. GPR tests were carried out on a variety of portland cement concrete pavements and laboratory concrete specimens. Results indicated that the higher frequency GPR antennas were capable of detecting subsurface distress in two of the three pavement sites investigated. However, the GPR systems failed to detect distress in one pavement site that exhibited extensive cracking. Laboratory experiments indicated that moisture conditions in the cracked pavement probably explain the failure. Accurate surveys need to account for moisture in the pavement slab. Importantly, however, once the pavement site exhibits severe surface cracking, there is little need for GPR, which is primarily used to detect distress that is not observed visually. Two visual inspections were also conducted for this study by personnel from Mandli Communications, Inc., and the Iowa Department of Transportation (DOT). The surveys were conducted using an Iowa DOT video log van that Mandli had fitted with additional equipment. The first survey was an extended demonstration of the PPS system. The second survey utilized the PPS with a downward imaging system that provided high-resolution pavement images. Experimental difficulties occurred during both studies; however, enough information was extracted to consider both surveys successful in identifying pavement surface distress. The results obtained from both GPR testing and visual inspections were helpful in identifying sites that exhibited materials-related distress, and both were considered to have passed the proof-of-concept trials. However, neither method can currently diagnose materials-related distress. Both techniques only detected the symptoms of materials-related distress; the actual diagnosis still relied on coring and subsequent petrographic examination. Both technologies are currently in rapid development, and the limitations may be overcome as the technologies advance and mature.

Laboratory Performance Evaluation of CIR-Emulsion and its Comparison Against CIR-Foam Test Results from Phase 2, TR-474, 2009

Currently, no standard mix design procedure is available for CIR-emulsion in Iowa. The CIR-foam mix design process developed during the previous phase is applied for CIR-emulsion mixtures with varying emulsified asphalt contents. Dynamic modulus test, dynamic creep test, static creep test and raveling test were conducted to evaluate the short- and long-term performance of CIR-emulsion mixtures at various testing temperatures and loading conditions. A potential benefit of this research is a better understanding of CIR-emulsion material properties in comparison with those of CIR-foam material that would allow for the selection of the most appropriate CIR technology and the type and amount of the optimum stabilization material. Dynamic modulus, flow number and flow time of CIR-emulsion mixtures using CSS- 1h were generally higher than those of HFMS-2p. Flow number and flow time of CIR-emulsion using RAP materials from Story County was higher than those from Clayton County. Flow number and flow time of CIR-emulsion with 0.5% emulsified asphalt was higher than CIR-emulsion with 1.0% or 1.5%. Raveling loss of CIR-emulsion with 1.5% emulsified was significantly less than those with 0.5% and 1.0%. Test results in terms of dynamic modulus, flow number, flow time and raveling loss of CIR-foam mixtures are generally better than those of CIR-emulsion mixtures. Given the limited RAP sources used for this study, it is recommended that the CIR-emulsion mix design procedure should be validated against several RAP sources and emulsion types.

Total Cost of Transportation Analysis of Road and Highway Issues, TR-477, Phase 2, 2003

A prior project, HR-388, (which was entitled "Total Cost of Transportation analysis of road and highway issues"), explored the use of a total economic cost basis for evaluation of road based transportation issues. It was conducted as a proof-of-concept effort between 1996 and 2002, with the final report presented in May 2002. TR-477 rebuilt the analytical model using current data, then performed general, system level, county level, and road segment level analyses. The results are presented herein and will be distributed to all county engineers for information and local use.

Ultraweak photon emission in assessing bone growth factor efficiency using fibroblastic differentiation.

Photons participate in many atomic and molecular interactions and changes. Recent biophysical research has shown the induction of ultraweak photons in biological tissue. It is now established that plants, animal and human cells emit a very weak radiation which can be readily detected with an appropriate photomultiplier system. Although the emission is extremely low in mammalian cells, it can be efficiently induced by ultraviolet light. In our studies, we used the differentiation system of human skin fibroblasts from a patient with Xeroderma Pigmentosum of complementation group A in order to test the growth stimulation efficiency of various bone growth factors at concentrations as low as 5 ng/ml of cell culture medium. In additional experiments, the cells were irradiated with a moderate fluence of ultraviolet A. The different batches of growth factors showed various proliferation of skin fibroblasts in culture which could be correlated with the ultraweak photon emission. The growth factors reduced the acceleration of the fibroblast differentiation induced by mitomycin C by a factor of 10-30%. In view that fibroblasts play an essential role in skin aging and wound healing, the fibroblast differentiation system is a very useful tool in order to elucidate the efficacy of growth factors.

Road Safety Audits for County Road X-23 from IA 2 to the South Corporate Limits of West Point and for County Road W-62 from US 218 to IA 27 in Lee County, Iowa, 2010

On October 20–21, 2009, two road safety audits were conducted in Lee County, Iowa: one for a 6 mile section of County Road X-23 from IA 2 to the south corporate limits of West Point and one for a 9.7 mile section of County Road W-62 from US 218 to IA 27. Both roads have high severe crash histories for the years of 2001 through 2008. Using these crash data, the Iowa Department of Transportation (Iowa DOT) has identified County Road X-23 as being in the top 5 percent of similar roads for run-off-road crashes. The Iowa DOT lists County Road W-62 as a high-risk rural road that has above-average crash numbers and is eligible for funding under the Federal High-Risk Rural Road Program. Considering these issues, the Lee County Engineer and Iowa DOT requested that road safety audits be conducted to address the safety concerns and to suggest possible mitigation strategies.