Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer

In patients with colorectal cancer (CRC), local and systemic inflammatory responses have been extensively reported to associate with cancer survival. However, the specific signalling pathways responsible for inflammatory responses are not clear. The PTEN/Akt pathway is a plausible candidate as it may play a role in mediating inflammation via COX-2, and has been associated with cancer progression. This study therefore examined the relationship between tumour PTEN/Akt/COX-2 expression, inflammatory responses and survival in CRC patients using a tissue microarray. In 201 CRC patients, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (12.0yrs v 7.3yrs, P=0.032), poorer differentiation (P=0.032), venous invasion (P=0.008) and peritoneal involvement (P=0.004). Patients were stratified for peri-nuclear expression of COX-2 to examine associations with inflammatory responses. In patients with absent peri-nuclear COX-2 expression, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (11.9yrs v 5.4yrs, P=0.001), poorer differentiation (P=0.018), venous invasion (P=0.003) and peritoneal involvement (P=0.001). However, no associations were seen with either the local or systemic inflammatory responses. In CRC patients, tumour-specific PTEN/Akt pathway activation was significantly associated with poorer CSS, particularly when peri-nuclear COX-2 expression was absent. However, activation of the PTEN/Akt pathway appears not to be responsible for the regulation of inflammatory responses

Quality and Severity of Lower Urinary Tract Symptoms among African American Elders

Lack of population-based data on lower urinary tract symptoms (LUTS) among African American men represents a significant gap in understanding. This study examined LUTS among a racially over-sampled, mixed urban/rural, elderly cohort of African Americans and whites in the South to discern whether racial differences exist in the prevalence, severity, and associated risk factors of LUTS. Longitudinal analyses using generalized estimating equations (GEE) were conducted on the 1994–1998 EPESE dataset for 5 North Carolina counties. In 1994, the analytic cohort included 482 African Americans and 407 whites; by 1998, 249 and 222, respectively. In 1994, 49.4% of African Americans reported LUTS compared to 56.8% of whites. By 1998, percentages increased to 60.6% and 70.3%, respectively. LUTS was associated with being African American, married, having poor health status and disability, delaying care quite often, being in a nursing home or in a rural area, and having a male physician

The relationship between members of the canonical NF-κB pathway, components of tumour microenvironment and survival in patients with invasive ductal breast cancer

The aim of the present study was to examine the relationship between tumour NF-κB activation, tumour microenvironment including local inflammatory response (LIR) and cancer-specific survival in patients with operable ductal breast cancer. Immunohistochemistry (tissue microarray of 376 patients) and western blotting (MCF7 and MDA-MB-231 breast cancer cells) was performed to assess expression of key members of the canonical NF-κB pathway (inhibitory kappa B kinase (IKKβ) and phosphorylated p65 Ser-536 (p-p65)). Following silencing of IKKβ, cell viability and apoptosis was assessed in both MCF7 and MDA-MB-231 cell lines. P-p65 was associated with cancer-specific survival (CSS) (nuclear P=0.042 and total P=0.025). High total p-p65 was associated with increase grade tumour grade (P=0.010), ER positivity (P=0.023), molecular subtype (P=0.005), lower Klintrup- Makinen grade (P=0.013) and decreased CD138 count (P=0.032). On multivariate analysis, total p-p65 expression independently associated with poorer CSS (P=0.020). In vitro work demonstrated that the canonical NF-κB pathway was inducible by exposure to TNFα in ER-positive MCF7 cells and to a lesser extent in ER-negative MDAMB- 231 cells. Reduction of IKKβ expression by siRNA transfection increased levels of apoptosis and reduced cell viability in both MCF7 (P= 0.001, P=0.002, respectively). This is consistent with the hypothesis that canonical IKKβ-NF-κB signalling drives tumour survival. These results suggest that activation of the canonical NF-κB pathway is an important determinant of poor outcome in patients with invasive ductal breast cancer

Adiabatic Quantum Computing for Random Satisfiability Problems

The discrete formulation of adiabatic quantum computing is compared with other search methods, classical and quantum, for random satisfiability (SAT) problems. With the number of steps growing only as the cube of the number of variables, the adiabatic method gives solution probabilities close to 1 for problem sizes feasible to evaluate via simulation on current computers. However, for these sizes the minimum energy gaps of most instances are fairly large, so the good performance scaling seen for small problems may not reflect asymptotic behavior where costs are dominated by tiny gaps. Moreover, the resulting search costs are much higher than for other methods. Variants of the quantum algorithm that do not match the adiabatic limit give lower costs, on average, and slower growth than the conventional GSAT heuristic method.Comment: added discussion of discrete adiabatic method, and simulations with 30 bits 8 pages, 8 figure

War and the Reelection Motive: Examining the Effect of Term Limits

This article investigates the relationship between term limits and international conflict. Theories of political survival and diversionary war both imply term limits should play a role in international relations, whereas “permanent referendum theory,” largely motivated by work in American politics, suggests otherwise. Drawing on these theories, we formulate and test competing hypotheses regarding term limits and international crises. Using dyadic militarized interstate disputes data and information on forty-eight democracies with term limits, we uncover strong evidence to support the claim that leaders reaching final terms in office are more likely to initiate conflict than those still subject to reelection. Moreover, we find that the likelihood of conflict initiation is significantly higher during times of recession, but only in the absence of binding term limits. While binding electoral terms and economic downturns are both independently associated with increased levels of conflict initiation, in concert their conditional effects actually counteract each other

Early diagenetic vivianite [Fe-3(PO4)(2) center dot 8H(2)O] in a contaminated freshwater sediment and insights into zinc uptake: a mu-EXAFS, mu-XANES and Raman study

The sediments in the Salford Quays, a heavily-modified urban water body, contain high levels of organic matter, Fe, Zn and nutrients as a result of past contaminant inputs. Vivianite [Fe3(PO4)2 · 8H2O] has been observed to have precipitated within these sediments during early diagenesis as a result of the release of Fe and P to porewaters. These mineral grains are small (<100 μm) and micron-scale analysis techniques (SEM, electron microprobe, μ-EXAFS, μ-XANES and Raman) have been applied in this study to obtain information upon the structure of this vivianite and the nature of Zn uptake in the mineral. Petrographic observations, and elemental, X-ray diffraction and Raman spectroscopic analysis confirms the presence of vivianite. EXAFS model fitting of the FeK-edge spectra for individual vivianite grains produces Fe–O and Fe–P co-ordination numbers and bond lengths consistent with previous structural studies of vivianite (4O atoms at 1.99–2.05 Å; 2P atoms at 3.17–3.25 Å). One analysed grain displays evidence of a significant Fe3+ component, which is interpreted to have resulted from oxidation during sample handling and/or analysis. EXAFS modelling of the Zn K-edge data, together with linear combination XANES fitting of model compounds, indicates that Zn may be incorporated into the crystal structure of vivianite (4O atoms at 1.97 Å; 2P atoms at 3.17 Å). Low levels of Zn sulphate or Zn-sorbed goethite are also indicated from linear combination XANES fitting and to a limited extent, the EXAFS fitting, the origin of which may either be an oxidation artifact or the inclusion of Zn sulphate into the vivianite grains during precipitation. This study confirms that early diagenetic vivianite may act as a sink for Zn, and potentially other contaminants (e.g. As) during its formation and, therefore, forms an important component of metal cycling in contaminated sediments and waters. Furthermore, for the case of Zn, the EXAFS fits for Zn phosphate suggest this uptake is structural and not via surface adsorption

High-temperature ferromagnetism of spsp electrons in narrow impurity bands: Application to CaB6_6

Ferromagnetism with high Curie temperature $T_c$, well above room temperature, and very small saturation moment has been reported in various carbon and boron systems. It is argued that the magnetization must be very inhomogeneous with only a small fraction of the sample ferromagnetically ordered. It is shown that a possible source of high $T_c$ within the ferromagnetic regions is itinerant electrons occupying a narrow impurity band. Correlation effects do not reduce the effective interaction which enters the Stoner criterion in the same way as in a bulk band. It is also shown how, in the impurity band case, spin wave excitations may not be effective in lowering $T_c$ below its value given by Stoner theory. These ideas are applied to CaB$_6$ and a thorough review of the experimental situation in this material is given. It is suggested that the intrinsic magnetism of the B$_2$ and O$_2$ dimers might be exploited in suitable structures containing these elements.Comment: 26 pages, 2 figure

Neuropsychological Assessment, Neuroimaging, and Neuropsychiatric Evaluation in Pediatric and Adult Patients with Sickle Cell Disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities

Relationships of the Psychological Influence of Food and Barriers to Lifestyle Change to Weight and Utilization of Online Weight Loss Tools

Abstract: Introduction: The psychological influence of food (PFS) and perceived barriers to lifestyle change (PBLC) were considered as predictors of body mass index and website tool utilization (TU) in an online weight loss program. Materials and Methodology: An archival analysis of all (N = 1361) overweight/obese (BMI M = 31.6 + 6.24 kg/m 2), adult (M = 42.0 + 10.72 years) users (82.4 % female) of an evidence-based, multidisciplinary Internet weight loss program was performed. Predictor variables included: PFS and PBLC, age, and longest maintained weight loss in relation to 1) BMI 2

Constraints on Evolutionary Properties of GHz Peaked Spectrum Galaxies

We have used the available samples of Gigahertz Peaked Spectrum (GPS) galaxies to investigate their evolution properties in the framework of the ``youth'' scenario. Care was taken to properly allow for the different selection criteria used to define the samples. We find that the observed redshift and peak frequency distributions can be satisfactorily accounted for in terms of simple luminosity evolution of individual sources, along the lines discussed by Fanti et al. (1995) and Begelman (1996, 1999), although the derived parameter values have large uncertainties due to ambiguities in the selection of GPS sources and to the incompleteness of redshift measurements. However the simplest self-similar model, whereby the evolution is controlled only by the radial profile of the density of the ambient medium is not good enough and one additional parameter needs to be introduced. The fit requires a decrease of the emitted power and of the peak luminosity with source age or with decreasing peak frequency, at variance with the Snellen et al. (2000) model. On the other hand, our analysis confirms the rather flat slope of the luminosity function, found by Snellen et al. (2000) who also report indications of a high luminosity break, not required by the data sets we have used. Our results suggest that the GPS galaxies are the precursors of extended radio sources with luminosities below the break of the luminosity function. No cosmological evolution of the GPS galaxy population is required by presently available data.Comment: 12 pages, 5 figures, accepted for publication in Astronomy & Astrophysics. Figure 1 has been replace