Routine Screening for Abdominal Aortic Aneurysm: Is it for everyone?

Objective: Determine whether routine abdominal ultrasound screening in all men ages 65 and over, not just those who are symptomatic or at risk, would be beneficial in reducing the mortality rate from abdominal aortic aneurysms (AAA). Design: Systematic literature review. Methods: The clinical question investigated is whether routine ultrasound screening of AAA for men over age 65 reduces AAA-related mortality as compared to not routinely screening. Searches were done through PubMed using the keywords: screening, abdominal aortic aneurysm, reduce, and mortality. Citations used by the USPSTF AAA screening guidelines were also added to the literature search. In PubMed, further limitations were made by eliminating those that did not discuss screening and subsequent diagnosis of AAA, as well as full-text articles that did not discuss screening of males over 65 years old or if they were not clinical trials or systematic reviews. Eventually, only randomized controlled trials were included for analysis. Results: Randomized controlled trials conducted by Norman et al, Ashton et al, and Scott et al, were all chosen for analysis as they met the inclusion/exclusion criteria for the proposed clinical question. Studies by Norman et al, Ashton et al, and Scott et al estimated the numbers needed to screen at 1,393, 709, and 466 respectively. Conclusion: All of the studies clearly demonstrate a decrease in AAA-related mortality when routinely screening men greater than 65 years by ultrasound for AAA. However, the cost effectiveness of the suggested screening regimen as compared to the overall benefits of said screening warrants further investigation

Elimination kinetics of diisocyanates after specific inhalative challenges in humans: mass spectrometry analysis, as a basis for biomonitoring strategies

Background: Isocyanates are some of the leading occupational causes of respiratory disorders, predominantly asthma. Adequate exposure monitoring may recognize risk factors and help to prevent the onset or aggravation of these aliments. Though, the biomonitoring appears to be most suitable for exposure assessment, the sampling time is critical, however. In order to settle the optimal time point for the sample collection in a practical biomonitoring approach, we aimed to measure the elimination of isocyanate urine metabolites. Methods: A simple biomonitoring method enabling detection of all major diamine metabolites, from mono-, poly- and diisocyanates in one analytical step, has been established. Urine samples from 121 patients undergoing inhalative challenge tests with diisocyanates for diagnostic reasons were separated by gas chromatography and analyzed with mass spectrometry (GC-MS) at various time points (0-24 h) after the onset of exposure. Results: After controlled exposures to different concentrations of diisocyanates (496 +/- 102 ppb-min or 1560 +/- 420 ppb-min) the elimination kinetics (of respective isocyanate diamine metabolites) revealed differences between aliphatic and aromatic isocyanates (the latter exhibiting a slower elimination) and a dose-response relationship. No significant differences were observed, however, when the elimination time patterns for individual isocyanates were compared, in respect of either low or high exposure or in relation to the presence or absence of prior immunological sensitization. Conclusions: The detection of isocyanate metabolites in hydrolyzed urine with the help of gas chromatography combined with mass spectrometric detection system appears to be the most suitable, reliable and sensitive method to monitor possible isocyanate uptake by an individual. Additionally, the information on elimination kinetic patterns must be factored into estimates of isocyanate uptake before it is possible for biomonitoring to provide realistic assessments of isocyanate exposure. The pathophysiological elimination of 1,6-hexamethylene diamine, 2,4-diamine toluene, 2,6-diamine toluene, 1,5-naphthalene diamine, 4,4'-diphenylmethane diamine and isophorone diamines (as respective metabolites of: 1,6-hexamethylene diisocyanate, 2,4-toluene diisocyanate and 2,6 toluene diisocyanate, 1,5-naphthalene diisocyanate, 4,4'-diphenylmethane diisocyanate and isophorone diisocyanates) differs between individual isocyanates' diamines

Lord of the Rings: A Kinematic Distance to Circinus X-1 from a Giant X-Ray Light Echo

Circinus X-1 exhibited a bright X-ray flare in late 2013. Follow-up observations with Chandra and XMM-Newton from 40 to 80 days after the flare reveal a bright X-ray light echo in the form of four well-defined rings with radii from 5 to 13 arcminutes, growing in radius with time. The large fluence of the flare and the large column density of interstellar dust towards Circinus X-1 make this the largest and brightest set of rings from an X-ray light echo observed to date. By deconvolving the radial intensity profile of the echo with the MAXI X-ray lightcurve of the flare we reconstruct the dust distribution towards Circinus X-1 into four distinct dust concentrations. By comparing the peak in scattering intensity with the peak intensity in CO maps of molecular clouds from the Mopra Southern Galactic Plane CO Survey we identify the two innermost rings with clouds at radial velocity ~ -74 km/s and ~ -81 km/s, respectively. We identify a prominent band of foreground photoelectric absorption with a lane of CO gas at ~ -32 km/s. From the association of the rings with individual CO clouds we determine the kinematic distance to Circinus X-1 to be $D_{Cir X-1} = 9.4^{+0.8}_{-1.0}$ kpc. This distance rules out earlier claims of a distance around 4 kpc, implies that Circinus X-1 is a frequent super-Eddington source, and places a lower limit of $\Gamma \gtrsim 22$ on the Lorentz factor and an upper limit of $\theta_{jet} \lesssim 3^{\circ}$ on the jet viewing angle.Comment: 20 pages, 21 figures, Astrophysical Journal, in prin

Thermoresponsive fluorinated small-molecule drugs: a new concept for efficient localized chemotherapy

Hyperthermia is currently being explored as an adjuvant treatment to conventional therapies with chemotherapeutic agents based on thermoresponsive macromolecules. Although the concept of hyperthermia has existed for many years it has yet to become routinely used in the clinical management of cancer. The development of small thermoresponsive molecules could help to change this paradigm. Temperaturesensitive compounds have recently been developed by covalently modifying drug and drug-like molecules with thermomorphic perfluorinated appendages. Lead thermoresponsive compounds have been validated in a pre-clinical model, displaying high tumor growth inhibition, with strong synergies observed between hyperthermia and the thermomorphic compounds

Thermoresponsive organometallic arene ruthenium complexes for tumour targeting

Application of mild hyperthermia can increase the cytotoxicity of anticancer drugs in tumour cells. In this report, we describe low molecular weight thermoactive ruthenium-based drugs with fluorous chains that are selectively triggered by mild hyperthermia. The organometallic complexes were prepared, characterized, and evaluated for their in vitro cytotoxicity against a panel of human cancer cell lines and non-cancerous immortalized cells. The compounds show considerable chemo-thermal selectivity towards cancer cells (ca. 5 mu M versus >500 mu M for healthy cells) for the compound with the longest fluorous chain

In vivo evaluation of small-molecule thermoresponsive anticancer drugs potentiated by hyperthermia

Hyperthermia used as an adjuvant with chemotherapy is highly promising in the treatment of certain cancers. Currently, the small molecule drugs used in combination with hyperthermia were not designed for this application. Herein, we report the evaluation of a chlorambucil and a ruthenium compound modified with a long fluorous chain, which exhibit thermoresponsive activity in colorectal adenocarcinoma xenografts in athymic mice in combination with mild hyperthermia (42 degrees C). Intraperitoneal injection of the derivatives followed by local hyperthermia showed a synergistic tumor growth reduction by 79% and 90% for the chlorambucil and ruthenium-based derivatives, respectively, with the latter exhibiting a higher synergy in combination with hyperthermia compared to the monotherapies. Histological analysis shows that both derivatives in combination with hyperthermia significantly decrease the number of proliferating tumor cells

Positivity of the English language

Over the last million years, human language has emerged and evolved as a fundamental instrument of social communication and semiotic representation. People use language in part to convey emotional information, leading to the central and contingent questions: (1) What is the emotional spectrum of natural language? and (2) Are natural languages neutrally, positively, or negatively biased? Here, we report that the human-perceived positivity of over 10,000 of the most frequently used English words exhibits a clear positive bias. More deeply, we characterize and quantify distributions of word positivity for four large and distinct corpora, demonstrating that their form is broadly invariant with respect to frequency of word use.Comment: Manuscript: 9 pages, 3 tables, 5 figures; Supplementary Information: 12 pages, 3 tables, 8 figure

Constraining Jet/Disk Geometry and Radiative Processes in Stellar Black Holes XTE J1118+480 and GX 339-4

We present results from modeling of quasi-simultaneous broad band (radio through X-ray) observations of the galactic stellar black hole (BH) transient X-ray binary (XRB) systems XTE J1118+480 and GX 339-4 using an irradiated disc + compact jet model. In addition to quantifying the physical properties of the jet, we have developed a new irradiated disc model which also constrains the geometry and temperature of the outer accretion disc by assuming a disc heated by viscous energy release and X-ray irradiation from the inner regions. For the source XTE J1118+480, which has better spectral coverage of the two in optical and near-IR (OIR) wavelengths, we show that the entire broad band continuum can be well described by an outflow-dominated model + an irradiated disc. The best-fit radius of the outer edge of the disc is consistent with the Roche lobe geometry of the system, and the temperature of the outer edge of the accretion disc is similar to those found for other XRBs. Irradiation of the disc by the jet is found to be negligible for this source. For GX 339-4, the entire continuum is well described by the jet-dominated model only, with no disc component required. For the two XRBs, which have very different physical and orbital parameters and were in different accretion states during the observations, the sizes of the jet base are similar and both seem to prefer a high fraction of non-thermal electrons in the acceleration/shock region and a magnetically dominated plasma in the jet. These results, along with recent similar results from modeling other galactic XRBs and AGNs, may suggest an inherent unity in diversity in the geometric and radiative properties of compact jets from accreting black holes.Comment: Accepted for publication in MNRAS. Uses mn2e.cls. 17 pages, 4 figures, 3 table