U.S.-Norway Comparison of Interval Breast Cancers

Background: Publications from the International Breast Screening Network (IBSN) have shown that varying definitions create hurdles for comparison of screening performance. Interval breast cancer rates are particularly affected. Objective: to test whether variations in definition of interval cancer rates (ICR) affect comparisons of international ICR, specific to a comparison of ICR in Norway and North Carolina (NC). Methods: An interval cancer (IC) was defined as a cancer diagnosed following a negative screening mammogram in a defined follow-up period. ICR was calculated for women ages 50-69, at subsequent screening in Norway and NC, during the time period 1996 - 2002. ICR was defined using three different denominators (negative screens, negative final assessments and all screens) and three different numerators (DCIS, invasive cancer and all cancers). ICR was then calculated with two methods: 1) number of ICs divided by the number of screens, and ICs divided by the number of women-years at risk for IC. Results: There were no differences in ICR depending on the definition used. In the 1-12 month follow up period ICR (based on number of screens) were: 0.53, 0.54, and 0.54 for Norway; and 1.20, 1.25 and 1.17 for NC, for negative screens, negative final assessment and all screens, respectively: The same trend was seen for 13-24 and 1-24 months follow-up. Using women-years for the analysis did not change the trend. ICR was higher in NC compared to Norway under all definitions and in all follow-up time periods, regardless of calculation method. Conclusion: The ICR within or between Norway and NC did not differ by definition used. ICR were higher in NC than Norway. There are many potential explanations for the difference.

A comparative long-memory Analysis between Spanish, Mexican and U.S. interest rates

Evidence exists that many natural facts are described better as a fractal. Although fractals are very useful for describing nature, it is also appropiate to review the concept of random fractal in finance. Due to the extraordinary importance of Brownian motion in physics, chemistry or biology, we will consider the generalization that supposes fractional Brownian motion introduced by Mandelbrot.The main goal of this work is to analyse the existence of long range dependence in instantaneous forward rates of different financial markets. Concretelly, we perform an empirical analysis on the Spanish, Mexican and U.S. interbanking interest rate. We work with three time series of daily data corresponding to 1 day operations from 28th March 1996 to 21st May 2002. From among all the existing tests on this matter we apply the methodology proposed in Taqqu, Teverovsky and Willinger (1995).

Missouri River Flood Coordination Task Force Report, September 25, 2011

The Missouri River floods of 2011 will go down in history as the longest duration flooding event this state has seen to date. The combination of above normal snowfall in the upper Missouri River basin followed by the equivalent of nearly one year’s worth of rainfall in May created an above normal runoff situation which filled the Missouri River and the six main reservoirs within the basin. Compounding this problem was colder than normal temperatures which kept much of the snowpack in the upper basin on the ground longer into the spring, setting the stage for this historic event. The U.S. Army Corps of Engineers (USACE) began increasing the outflow at Gavin’s Point, near Yankton, South Dakota in May. On June 14, 2011, the outflow reached a record rate of over 160,000 cubic feet per second (cfs), over twice the previous record outflow set in 1997. This increased output from Gavin’s Point caused the Missouri River to flow out of its banks covering over 283,000 acres of land in Iowa, forcing hundreds of evacuations, damaging 255,000 acres of cropland and significantly impacting the levee system on the Missouri River basin. Over the course of the summer, approximately 64 miles of primary roads closed due to Missouri River flooding, including 54 miles of Interstate Highway. Many county secondary roads were closed by high water or overburdened due to the numerous detours and road closures in this area. As the Missouri River levels began to increase, municipalities and counties aided by State and Federal agencies began preparing for a sustained flood event. Citizens, businesses, state agencies, local governments and non‐profits made substantial preparations, in some cases expending millions of dollars on emergency protective measures to protect their facilities from the impending flood. Levee monitors detected weak spots in the levee system in all affected counties, with several levees being identified as at risk levees that could potentially fail. Of particular concern was the 28 miles of levees protecting Council Bluffs. Based on this concern, Council Bluffs prepared an evacuation plan for the approximately 30,000 residents that resided in the protected area. On May 25, 2011, Governor Branstad directed the execution of the Iowa Emergency Response Plan in accordance with Section 401 of the Stafford Act. On May 31, 2011, HSEMD Administrator, Brigadier General J. Derek Hill, formally requested the USACE to provide technical assistance and advanced measures for the communities along the Missouri River basin. On June 2, 2011 Governor Branstad issued a State of Iowa Proclamation of Disaster Emergency for Fremont, Harrison, Mills, Monona, Pottawattamie, and Woodbury counties. The length of this flood event created a unique set of challenges for Federal, State and local entities. In many cases, these organizations were conducting response and recovery operations simultaneously. Due to the length of this entire event, the State Emergency Operations Center and the local Emergency Operations Centers remained open for an extended period of time, putting additional strain on many organizations and resources. In response to this disaster, Governor Branstad created the Missouri River Recovery Coordination Task Force to oversee the State’s recovery efforts. The Governor announced the creation of this Task Force on October 17, 2011 and appointed Brigadier General J. Derek Hill, HSEMD Administrator as the chairman. This Task Force would be a temporary group of State agency representatives and interested stakeholders brought together to support the recovery efforts of the Iowa communities impacted by the Missouri River Flood. Collectively, this group would analyze and share damage assessment data, coordinate assistance across various stakeholders, monitor progress, capture best practices and identify lessons learned.

Systemic vascular dysfunction in patients with chronic mountain sickness.

ABSTRACT BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, these patients often present functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients suffering from diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS display systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity. METHODS: To test this hypothesis, we assessed systemic endothelial function (by flow- mediated dilation, FMD), arterial stiffness and carotid intima-media thickness and arterial oxygenation (SaO(2)) in 23 patients with CMS without additional classical cardiovascular risk factors and 27 age-matched healthy mountain dwellers born and permanently living at 3600 m. For some analyses subjects were classified according to baseline SaO(2) quartiles; FMD of the highest quartile subgroup (SaO(2) ≥90%) was used as reference value for post-hoc comparisons. RESULTS: Patients with CMS displayed marked systemic vascular dysfunction, as evidenced by impaired FMD (4.6±1.2 vs. 7.6±1.9%, CMS vs. controls, P<0.0001), greater pulse wave velocity (10.6±2.1 vs. 8.4±1.0 m/s, P<0.001) and carotid intima-media thickness (690±120 vs. 570±110 μm, P=0.001). A positive relationship existed between SaO(2) and FMD (r=0.62, P<0.0001). Oxygen inhalation improved (P<0.001), but did not normalize FMD in patients with CMS; whereas it normalized FMD in hypoxemic controls (SaO(2) <90%) and had no detectable effect in normoxemic (SaO(2) ≥90%) control subjects. CONCLUSIONS: Patients with CMS display marked systemic vascular dysfunction. Structural and functional alterations contribute to this problem that may predispose these patients to premature cardiovascular disease. Clinical Trials Gov Registration # NCT01182792.

Recent misconceptions about the "database search problem": a probabilistic analysis using Bayesian networks

This paper analyses and discusses arguments that emerge from a recent discussion about the proper assessment of the evidential value of correspondences observed between the characteristics of a crime stain and those of a sample from a suspect when (i) this latter individual is found as a result of a database search and (ii) remaining database members are excluded as potential sources (because of different analytical characteristics). Using a graphical probability approach (i.e., Bayesian networks), the paper here intends to clarify that there is no need to (i) introduce a correction factor equal to the size of the searched database (i.e., to reduce a likelihood ratio), nor to (ii) adopt a propositional level not directly related to the suspect matching the crime stain (i.e., a proposition of the kind 'some person in (outside) the database is the source of the crime stain' rather than 'the suspect (some other person) is the source of the crime stain'). The present research thus confirms existing literature on the topic that has repeatedly demonstrated that the latter two requirements (i) and (ii) should not be a cause of concern.

[Voyage en Italie : 1824-1830]. , Tombeau de Bibulus à Rome. Détails au quart de l'exéc[u]tion : [détail d'élévation de la frise, avec entablement et chapiteau, détail d'élévation de la base d'une colonne, deux profils] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 606

Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.

Vascular dysfunction in offspring of preeclampsia is related to preeclampsia per se rather than genetically determined

Objectives: Epidemiological studies suggest that adverse events in utero may predispose to premature cardiovascular disease in adulthood, but the mechanisms are not known. Recently, we found that young apparently healthy offspring of mothers with preeclampsia (PE) display systemic endothelial dysfunction. This problem could be related to PE per se or to a genetic abnormality that predisposes the mother to PE and the offspring to vascular dysfunction. To distinguish between these two possibilities, we assessed vascular function in offspring of PE, their siblings who were born after a normal pregnancy, and in control subjects.Methods: We measured endothelium-dependent vasodilation (flow-mediated vasodilation, FMD), in 10 pairs of healthy normotensive siblings, one born after PE (age 15±6 y; mean±SD), the other after normal pregnancy (17±6y) and in 17 (16±7y) controls. All subjects were born at term.Results: The vascular function in siblings of PE who were born after normal pregnancy was normal and comparable to the one in controls (8.6±1.5% vs. 8.1±1.3%, P=0.32), whereas offspring of PE displayed a roughly 30% smaller FMD than the two other groups (5.9±1.6%, P<0.005 vs. both siblings and controls, Figure). The endothelial dysfunction in the offspring of PE was not related to a difference in the central arterial blood pressure or arterial oxygen saturation, because they were comparable in the 3 groups. Figure 1. FMD in the three groups.Conclusions: These findings provide the first evidence that vascular dysfunction in offspring of PE is caused by PE itself, rather than by a genetic abnormality that predisposes the mother to PE and the offspring to a vascular defect. Prevention of PE and/or its successful treatment is expected to prevent vascular dysfunction and premature cardiovascular morbidity and mortality in the offspring.

Perceived discrimination against diabetics in the workplace and in work-related insurances in Switzerland.

To investigate the prevalence and risk factors of perceived diabetes-related discrimination in the workplace and in work-related insurances in persons with diabetes mellitus in Switzerland. 509 insulin-treated diabetic subjects representative of the northwestern Swiss population responded to a self-report questionnaire on perceived diabetes-related discrimination in the workplace and in work-related insurances (salary loss insurance, supplementary occupational plan). Discrimination was defined as being treated differently at least once in relation to diabetes. The reported rates of different aspects of discrimination in the workplace and in work-related insurances ranged between 5-11% and 4-15% respectively. Risk factors that independently increased the risk of not being hired due to diabetes were the presence of at least two severe hypoglycaemic events/year and relevant diabetic complications (OR 5.6 and OR 2.6 respectively; both<0.05). The presence of at least two severe hypoglycaemic events/year was also associated with an increased risk of losing one's job (OR 6.5, <0.01). Overweight or obesity were related to increased discrimination in work-related insurances (OR for denial 2.1-2.4; OR for reserve 3.9-4.4; all<0.05). Perceived diabetes-related discrimination in the workplace and by work-related insurances is a common problem. In the light of our findings the introduction of effective non-discrimination legislation for patients with chronic illnesses appears to be desirable.

Termination of major ductile strike-slip shear and differential cooling along the Insubric line (Central Alps): U-Pb, Rb-Sr and 40Ar/39Ar ages of cross-cutting pegmatites

To constrain the age of strike-slip shear, related granitic magmatism, and cooling along the Insubric line, 29 size fractions of monazite and xenotime were dated by the U-Pb method, and a series of 25 Rb-Sr and Ar-40/Ar-39 ages were measured on different size fractions of muscovite and biotite. The three pegmatitic intrusions analyzed truncate high-grade metamorphic mylonite gneisses of the Simplon shear zone, a major Alpine structure produced in association with dextral strike-slip movements along the southern edge of the European plate, after collision with its Adriatic indenter. Pegmatites and aplites were produced between 29 and 25 Ma in direct relation to right-lateral shear along the Insubric line, by melting of continental crust having Sr-87/Sr-86 between 0.7199 and 0.7244 at the time of melting. High-temperature dextral strike-slip shear was active at 29.2 +/- 0.2 (2 sigma) Ma, and it terminated before 26.4 +/- 0.1 Ma. During dike injection, temperatures in the country rocks of the Isorno-Orselina and Monte Rosa structural units did not exceed approximate to 500 degrees C, leading to fast initial cooling, followed by slower cooling to approximate to 350 degrees C within several million years. In one case, initial cooling to approximate to 500 degrees C was significantly delayed by about 4 m.y., with final cooling to approximate to 300 degrees C at 20-19 Ma in all units. For the period between 29 and 19 Ma, cooling of the three sample localities was non-uniform in space and time, with significant variations on the kilometre scale. These differences are most likely due to strongly varying heat flow, and/or heterogeneous distribution of unroofing rates within the continuously deforming Insubric line. If entirely ascribed to differences in unroofing, corresponding rates would vary between 0.5 and 2.5 mm/y, for a thermal gradient of 30 degrees/km.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Stochastic delay differential equations driven by fractional Brownian motion with Hurst parameter H 1/2

We consider the Cauchy problem for a stochastic delay differential equation driven by a fractional Brownian motion with Hurst parameter H>¿. We prove an existence and uniqueness result for this problem, when the coefficients are sufficiently regular. Furthermore, if the diffusion coefficient is bounded away from zero and the coefficients are smooth functions with bounded derivatives of all orders, we prove that the law of the solution admits a smooth density with respect to Lebesgue measure on R.

Governor's Office of Drug Control Policy Five-Year Strategic Plan July 1, 2010-June 30, 2015

The Office of the Drug Policy Coordinator is established in Chapter 80E of the Code of Iowa. The Coordinator directs the Governor’s Office of Drug Control Policy; coordinates and monitors all statewide counter-drug efforts, substance abuse treatment grants and programs, and substance abuse prevention and education programs; and engages in other related activities involving the Departments of public safety, corrections, education, public health, and human services. The coordinator assists in the development of local and community strategies to fight substance abuse, including local law enforcement, education, and treatment activities. The Drug Policy Coordinator serves as chairperson to the Drug Policy Advisory Council. The council includes the directors of the departments of corrections, education, public health, public safety, human services, division of criminal and juvenile justice planning, and human rights. The Council also consists of a prosecuting attorney, substance abuse treatment specialist, substance abuse prevention specialist, substance abuse treatment program director, judge, and one representative each from the Iowa Association of Chiefs of Police and Peace Officers, the Iowa State Police Association, and the Iowa State Sheriff’s and Deputies’ Association. Council members are appointed by the Governor and confirmed by the Senate. The council makes policy recommendations related to substance abuse education, prevention, and treatment, and drug enforcement. The Council and the Coordinator oversee the development and implementation of a comprehensive State of Iowa Drug Control Strategy. The Office of Drug Control Policy administers federal grant programs to improve the criminal justice system by supporting drug enforcement, substance abuse prevention and offender treatment programs across the state. The ODCP prepares and submits the Iowa Drug and Violent Crime Control Strategy to the U.S. Department of Justice, with recommendations from the Drug Policy Advisory Council. The ODCP also provides program and fiscal technical assistance to state and local agencies, as well as program evaluation and grants management.

[Voyage en Italie : 1824-1830]. , Palais de la Chancellerie. Détails du Soubassement, au dixième de l'Exec[u]tion : [élévation partielle, profil] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 574