CT texture analysis can help differentiate between malignant and benign lymph nodes in the mediastinum in patients suspected for lung cancer

BACKGROUND: In patients with non-small-cell lung carcinoma NSCLC the lymph node staging in the mediastinum is important due to impact on management and prognosis. Computed tomography texture analysis (CTTA) is a postprocessing technique that can evaluate the heterogeneity of marked regions in images. PURPOSE: To evaluate if CTTA can differentiate between malignant and benign lymph nodes in a cohort of patients with suspected lung cancer. MATERIAL AND METHODS: With tissue sampling as reference standard, 46 lymph nodes from 29 patients were analyzed using CTTA. For each lymph node, CTTA was performed using a research software "TexRAD" by drawing a region of interest (ROI) on all available axial contrast-enhanced computed tomography (CT) slices covering the entire volume of the lymph node. Lymph node CTTA comprised image filtration-histogram analysis undertakes two stages: the first step comprised an application of a Laplacian of Gaussian filter to highlight fine to coarse textures within the ROI, followed by a quantification of textures via histogram analysis using mean gray-level intensity from the entire volume of the lymph nodes. RESULTS: CTTA demonstrated a statistically significant difference between the malignant and the benign lymph nodes (P = 0.001), and by binary logistic regression we obtained a sensitivity of 53% and specificity of 97% in the test population. The area under the receiver operating curve was 83.4% and reproducibility was excellent. CONCLUSION: CTTA may be helpful in differentiating between malignant and benign lymph nodes in the mediastinum in patients suspected for lung cancer, with a low intra-observer variance

Antecedents and consequences of effectuation and causation in the international new venture creation process

The selection of the entry mode in an international market is of key importance for the venture. A process-based perspective on entry mode selection can add to the International Business and International Entrepreneurship literature. Framing the international market entry as an entrepreneurial process, this paper analyzes the antecedents and consequences of causation and effectuation in the entry mode selection. For the analysis, regression-based techniques were used on a sample of 65 gazelles. The results indicate that experienced entrepreneurs tend to apply effectuation rather than causation, while uncertainty does not have a systematic influence. Entrepreneurs using causation-based international new venture creation processes tend to engage in export-type entry modes, while effectuation-based international new venture creation processes do not predetermine the entry mod

A comparison of self reported air pollution problems and GIS-modeled levels of air pollution in people with and without chronic diseases

<p>Abstract</p> <p>Objective</p> <p>To explore various contributors to people's reporting of self reported air pollution problems in area of living, including GIS-modeled air pollution, and to investigate whether those with respiratory or other chronic diseases tend to over-report air pollution problems, compared to healthy people.</p> <p>Methods</p> <p>Cross-sectional data from the Oslo Health Study (2000–2001) were linked with GIS-modeled air pollution data from the Norwegian Institute of Air Research. Multivariate regression analyses were performed. 14 294 persons aged 30, 40, 45, 60 or 75 years old with complete information on modeled and self reported air pollution were included.</p> <p>Results</p> <p>People who reported air pollution problems were exposed to significantly higher GIS-modeled air pollution levels than those who did not report such problems. People with chronic disease, reported significantly more air pollution problems after adjustment for modeled levels of nitrogen dioxides, socio-demographic variables, smoking, depression, dwelling conditions and an area deprivation index, even if they had a non-respiratory disease. No diseases, however, were significantly associated with levels of nitrogen dioxides.</p> <p>Conclusion</p> <p>Self reported air pollution problems in area of living are strongly associated with increased levels of GIS-modeled air pollution. Over and above this, those who report to have a chronic disease tend to report more air pollution problems in area of living, despite no significant difference in air pollution exposure compared to healthy people, and no associations between these diseases and NO₂. Studies on the association between self reported air pollution problems and health should be aware of the possibility that disease itself may influence the reporting of air pollution.</p

Depot-Dependent Effects of Adipose Tissue Explants on Co-Cultured Hepatocytes

We have developed an in vitro hepatocyte-adipose tissue explant (ATE) co-culture model enabling examination of the effect of visceral and subcutaneous adipose tissues on primary rat hepatocytes. Initial analyses of inflammatory marker genes were performed in fractionated epididymal or inguinal adipose tissues. Expressions of inflammation related genes (IL-6, TNF-α, COX-2) were higher in the inguinal than the epididymal ATE. Similarly, expressions of marker genes of macrophage and monocyte (MPEG-1, CD68, F4/80, CD64) were higher in the stromal vascular fraction (SVF) isolated from inguinal ATE than that from epididymal ATE. However, expressions of lipolysis related genes (ATGL, HSL, perilipin-1) were higher in the epididymal adipocytes than inguinal adipocytes. Moreover, secretion of IL-6 and PGE2 was higher from inguinal ATEs than from epididymal ATEs. There was a trend that the total levels of IL-6, TNF-α and PGE2 in the media from inguinal ATEs co-cultured with primary rat hepatocytes were higher than that in the media from epididymal ATEs co-cultured with hepatocytes, although the significant difference was only seen in PGE2. Lipolysis, measured as glycerol release, was similar in the ATEs isolated from inguinal and epididymal adipose tissues when cultured alone, but the glycerol release was higher in the ATEs isolated from epididymal than from inguinal adipose tissue when co-cultured with hepatocytes. Compared to epididymal ATEs, the ATEs from inguinal adipose tissue elicited a stronger cytotoxic response and higher level of insulin resistance in the co-cultured hepatocytes. In conclusion, our results reveal depot-dependent effects of ATEs on co-cultured primary hepatocytes, which in part may be related to a more pronounced infiltration of stromal vascular cells (SVCs), particularly macrophages, in inguinal adipose tissue resulting in stronger responses in terms of hepatotoxicity and insulin-resistance

The influence of cardiovascular morbidity on the prognosis in prostate cancer. Experience from a 12-year nationwide Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>To determine the impact of preexisting ischemic heart disease (IHD) and stroke on overall survival in prostate cancer patients.</p> <p>Methods</p> <p>We conducted a cohort study of patients with incident prostate cancer registered in the Danish Cancer Registry from 1997 through 2008. We identified patients diagnosed with IHD or stroke prior to the date of prostate cancer diagnosis in the Danish National Patient Registry. We constructed Kaplan-Meier curves to analyze time to death and Cox regression was used to estimate hazard ratios (HRs) to compare mortality rates by preexisting IHD or stroke status, adjusting for age, stage, comorbidity, and calendar period.</p> <p>Results</p> <p>Of 30,721 prostate cancer patients, 4,276 (14%) had preexisting IHD and 1,331 (4%) preexisting stroke. Crude 1- and 5-year survival rates were 85% and 44% in men without preexisting IHD or stroke, 81% and 36% in men with preexisting IHD, and 78% and 27% in men with preexisting stroke. Adjusted HRs were 1.05 (95% CI 1.00-1.10) for patients with IHD and 1.20 (95% CI 1.12-1.30) for patients with stroke compared with patients without preexisting IHD or stroke.</p> <p>Conclusions</p> <p>Preexisting IHD had minimal impact on mortality in prostate cancer patients, whereas overall mortality was 20% higher in prostate cancer patients with preexisting stroke compared to those without IHD or stroke. These results highlight the importance of differentiating between various comorbidities.</p

Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia

Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events

The Tissue-Specific Rep8/UBXD6 Tethers p97 to the Endoplasmic Reticulum Membrane for Degradation of Misfolded Proteins

The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation

Discordant effect of body mass index on bone mineral density and speed of sound

BACKGROUND: Increased BMI may affect the determination of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) and speed of sound (SOS) measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI) on BMD and SOS measured along bones. METHODS: We compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m(2)), and 11 lean (BMI = 21 kg/m(2)) postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover. RESULTS: Mean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 ± 0.82, -0.99 ± 0.52, P < 0.00001). Femoral neck BMD in the overweight – but not in the lean group highly correlated with BMI (R = 0.68. P < 0.0001). Mean SOS at all measurement sites was similar in both groups and did not correlate with BMI. Bone turnover was similar in the two study groups. CONCLUSIONS: The high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women

Psoriasin (S100A7) expression is altered during skin tumorigenesis

BACKGROUND: Psoriasin (S100A7) expression has previously been associated with psoriasiform hyperplasia as well as with tumor progression in breast cancer. Its expression profile for different stages of skin lesions is unknown. The aim of this study was to determine the relationship between psoriasin (S100A7) and tumor progression in skin. METHODS: Psoriasin was assessed by immunohistochemistry and levels of expression determined by semi-quantitative scoring in skin biopsies from 50 patients. The cohort included normal skin, actinic keratosis, squamous carcinoma in-situ, invasive squamous cell carcinoma, and basal cell carcinoma. RESULTS: In normal skin, psoriasin was rarely detected in epidermis but was expressed in underlying adnexae. In abnormal epidermis psoriasin was frequently expressed in abnormal keratinocytes in actinic keratosis, in-situ and invasive squamous cell carcinoma, but was rarely observed in the basal epidermal layer or in superficial or invasive basal cell carcinoma. The highest levels of expression were seen within squamous carcinoma in-situ. Significantly reduced levels of expression were observed in both unmatched (p = 0.0001) and matched (p < 0.004) invasive squamous cell carcinoma. Psoriasin expression within abnormal squamous lesions correlated with mitotic count (r = 0.54, p = 0.0036), however no significant relation was found with the intensity of dermal inflammatory cell infiltrates assessed within each pathology. CONCLUSION: These results suggest that altered psoriasin expression occurs in abnormal epidermis and that downregulation may be related to the onset of invasion in squamous cell carcinoma in skin