Serum Dioxin, Testosterone, and Subsequent Risk of Benign Prostatic Hyperplasia: A Prospective Cohort Study of Air Force Veterans

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962–1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73–0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels

Disfluency in dialogue:an intentional signal from the speaker?

Disfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue. © 2012 Psychonomic Society, Inc

In situ evidence for the structure of the magnetic null in a 3D reconnection event in the Earth's magnetotail

Magnetic reconnection is one of the most important processes in astrophysical, space and laboratory plasmas. Identifying the structure around the point at which the magnetic field lines break and subsequently reform, known as the magnetic null point, is crucial to improving our understanding reconnection. But owing to the inherently three-dimensional nature of this process, magnetic nulls are only detectable through measurements obtained simultaneously from at least four points in space. Using data collected by the four spacecraft of the Cluster constellation as they traversed a diffusion region in the Earth's magnetotail on 15 September, 2001, we report here the first in situ evidence for the structure of an isolated magnetic null. The results indicate that it has a positive-spiral structure whose spatial extent is of the same order as the local ion inertial length scale, suggesting that the Hall effect could play an important role in 3D reconnection dynamics.Comment: 14 pages, 4 figure

An Approach for the Automated Generation of Engaging Dashboards

Organizations use Key Performance Indicators (KPIs) to monitor whether they attain their goals. To support organizations at tracking the performance of their business, software vendors offer dash boards to these organizations. For the development of the dashboards that will engage organizations and enable them to make informed deci sions, software vendors leverage dashboard design principles. However, the dashboard design principles available in the literature are expressed as natural language texts. Therefore, software vendors and organizations either do not use them or spend significant efforts to internalize and apply them literally in every engaging dashboard development process. We show that engaging dashboards for organizations can be automati cally generated by means of automatically visualized KPIs. In this con text, we present our novel approach for the automated generation of engaging dashboards for organizations. The approach employs the deci sion model for visualizing KPIs that is developed based on the dashboard design principles in the literature. We implemented our approach and evaluated its quality in a case study.Ministerio de Economía y Competitividad BELI (TIN2015-70560-R)Ministerio de Ciencia, Innovación y Universidades OPHELIA RTI2018-101204-B-C2

Nongenomic oestrogen signalling in oestrogen receptor negative breast cancer cells: a role for the angiotensin II receptor AT1

INTRODUCTION: Oestrogens can mediate some of their cell survival properties through a nongenomic mechanism that involves the mitogen-activated protein kinase (MAPK) pathway. The mechanism of this rapid signalling and its dependence on a membrane bound oestrogen receptor (ER), however, remains controversial. The role of G-protein-coupled receptor and epidermal growth factor (EGF) receptor in an ER-independent signalling pathway modulated by oestrogen was investigated. METHODS: ER-positive and ER-negative breast cancer cell lines (MCF-7 and SKBR3) and primary breast cancer cell cultures were used in this study. Cell proliferation was assessed using standard MTT assays. Protein and cAMP levels were detected by Western blotting and ELISA, respectively. Antigen localization was performed by immunocytochemistry, immunohistochemistry and immunofluorescence. Protein knockdown was achieved using small interfering RNA technologies. RESULTS: EGF and oestrogen, alone and in combination, induced cell proliferation and phosphorylation of MAPK proteins Raf and ERK (extracellular signal regulated kinase)1/2 in both ER-negative SKBR3 and ER-positive MCF-7 human breast cancer cell lines. Increased Raf phosphorylation was also observed in primary human breast cultures derived from ER-positive and ER-negative breast tumours. Oestrogen induced an increase in intracellular cAMP in ER-negative SKBR3 human breast cancer cells. Oestrogen-mediated cell growth and phosphorylation of MAPK was modified by the EGF receptor antagonist AG1478, the G-protein antagonist pertussis toxin, and the angiotensin II receptor antagonist saralasin. Knockdown of angiotensin II type 1 receptor (AT1) protein expression with small interfering RNA attenuated oestrogen-induced Raf phosphorylation in ER-negative cells. AT1 receptor was found to be expressed in the cell membrane of breast tumour epithelial cells. CONCLUSION: These findings provide evidence that, in breast cancer cells, oestrogen can signal through AT1 to activate early cell survival mechanisms in an ER-independent manner

Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

<p>Abstract</p> <p>Background</p> <p>Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV₁) (criterion validity) and change of %FEV₁(responsiveness) during treatment in pediatric patients with acute asthma exacerbations.</p> <p>Methods</p> <p>We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV₁, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests.</p> <p>Results</p> <p>We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV₁demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001).</p> <p>Conclusions</p> <p>PEP demonstrates criterion validity and responsiveness in correlations with %FEV₁. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus.</p

Mapping the proteo-genomic convergence of human diseases

Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries

Top quark forward-backward asymmetry in R-parity violating supersymmetry

The interaction of bottom squark-mediated top quark pair production, occurring in the R-parity violating minimal supersymmetric standard model (MSSM), is proposed as an explanation of the anomalously large $t\bar{t}$ forward-backward asymmetry (FBA) observed at the Tevatron. We find that this model can give a good fit to top quark data, both the inclusive and invariant mass-dependent asymmetries, while remaining consistent (at the 2-$\sigma$ level) with the total and differential production cross-sections. The scenario is challenged by strong constraints from atomic parity violation (APV), but we point out an extra diagram for the effective down quark-Z vertex, involving the same coupling constant as required for the FBA, which tends to weaken the APV constraint, and which can nullify it for reasonable values of the top squark masses and mixing angle. Large contributions to flavor-changing neutral currents can be avoided if only the third generation of sparticles is light.Comment: 24 pages, 7 figures. v3: included LHC top production cross section data; model still consistent at 2 sigma leve