Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index.

INTRODUCTION Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes. METHODS Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER-, PR-, HER2-, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER-, PR-, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER-, PR-, HER2-, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER-, PR-, HER2-, any Ki-67, CK 5/6-, EGFR-). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value. RESULTS Luminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months. CONCLUSIONS Each intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.

Ecological Footprint Inequality across countries: the role of environment intensity, income and interaction effects

Recently, White (2007) analysed the international inequalities in Ecological Footprints per capita (EF hereafter) based on a two-factor decomposition of an index from the Atkinson family (Atkinson (1970)). Specifically, this paper evaluated the separate role of environment intensity (EF/GDP) and average income as explanatory factors for these global inequalities. However, in addition to other comments on their appeal, this decomposition suffers from the serious limitation of the omission of the role exerted by probable factorial correlation (York et al. (2005)). This paper proposes, by way of an alternative, a decomposition of a conceptually similar index like Theil’s (Theil, 1967) which, in effect, permits clear decomposition in terms of the role of both factors plus an inter-factor correlation, in line with Duro and Padilla (2006). This decomposition might, in turn, be extended to group inequality components (Shorrocks, 1980), an analysis that cannot be conducted in the case of the Atkinson indices. The proposed methodology is implemented empirically with the aim of analysing the international inequalities in EF per capita for the 1980-2007 period and, amongst other results, we find that, indeed, the interactive component explains, to a significant extent, the apparent pattern of stability observed in overall international inequalities.

Prospective comparison of MR enteroclysis with multidetector spiral-CT enteroclysis: interobserver agreement and sensitivity by means of "sign-by-sign" correlation.

Our objective was a prospective comparison of MR enteroclysis (MRE) with multidetector spiral-CT enteroclysis (MSCTE). Fifty patients with various suspected small bowel diseases were investigated by MSCTE and MRE. The MSCTE was performed using slices of 2.5 mm, immediately followed by MRE, obtaining T1- and T2-weighted sequences, including gadolinium-enhanced acquisition with fat saturation. Three radiologists independently evaluated MSCTE and MRE searching for 12 pathological signs. Interobserver agreement was calculated. Sensitivities and specificities resulted from comparison with pathological results ( n=29) and patient's clinical evolution ( n=21). Most pathological signs, such as bowel wall thickening (BWT), bowel wall enhancement (BWE) and lymphadenopathy (ADP), showed better interobserver agreement on MSCTE than on MRE (BWT: 0.65 vs 0.48; BWE: 0.51 vs 0.37; ADP: 0.52 vs 0.15). Sensitivity of MSCTE was higher than that of MRE in detecting BWT (88.9 vs 60%), BWE (78.6 vs 55.5%) and ADP (63.8 vs 14.3%). Wilcoxon signed-rank test revealed significantly better sensitivity of MSCTE than that of MRE for each observer ( p=0.028, p=0.046, p=0.028, respectively). Taking the given study design into account, MSCTE provides better sensitivity in detecting lesions of the small bowel than MRE, with higher interobserver agreement.

Influència del clima en la fenologia de la floració de Globularia alypum: anàlisi a partir de mostres d'herbari

Globularia alypum és un arbust termòfil típic de la regió oest del Mediterrani. Aquest nanofaneròfit té un patró de floració molt ampli. Les poblacions primerenques floreixen des del Juliol fins al Desembre i les poblacions tardanes des del Gener fins a l’Abril. L’objectiu del projecte és esbrinar quins factors climàtics determinen la fenologia de la floració de l’espècie a partir de mostres d’herbari i conèixer l’abast geogràfic d’ambdós patrons de floració a la península Ibèrica i França. També l’estudi d’altres característiques fenològiques en relació amb el clima: els braquiblasts i les espigues de capítols. Els plecs d’herbari han estat georeferenciats per ser utilitzats en un entorn SIG junt amb les dades del clima i s’ha realitzat una anàlisi estadística. El resultats mostren que les poblacions primerenques creixen majoritàriament en zones costaneres mentre que les tardanes ho fan en zones continentals. Les poblacions primerenques creixen en àrees on les temperatures (mitjana, mínima, màxima i mínima del mes més fred) són més altes que les tardanes per l’efecte temperador del mar. Al analitzar totes les poblacions, el nombre de mesos des de la transició floral es correlaciona negativament amb la temperatura mínima mensual i la temperatura mitjana mensual en tots els mesos, mentre que amb la temperatura màxima mensual entre Octubre i Abril. Al estudiar sols les poblacions tardanes les correlacions són similars, però no en les primerenques on no se’n troba cap. Les correlacions entre el nombre de mesos des de la transició floral i les variables climàtiques anuals són iguals, a més de trobar-se una correlació negativa amb la temperatura mínima del mes més fred i l’índex tèrmic, i positiva amb l’índex de continentalitat. No s’ha trobat cap diferència en presència de braquiblasts segons la població, però sí en les espigues de capítols, essent més freqüents en les poblacions primerenques. Es suggereix que la temperatura és un factor més determinant per a les poblacions tardanes, mentre que es desconeix si és la precipitació en les primerenques. Tampoc es té coneixement sobre si les diferències entre els dos patrons són genètiques o fenotípiques i quin mecanisme possibilita el desenvolupament de braquiblasts i espigues de capítols.

ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

BACKGROUND Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. METHODS Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). RESULTS Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. CONCLUSION Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.

Solid pseudopapillary tumor of the pancreas in children: typical radiological findings and pathological correlation.

We report a case series of three children with solid pseudopapillary tumor of the pancreas (SPT) in which a complete radiological work-up, including ultrasound, computed tomography scans, and MRI, has been carried out. The aim of this article is to highlight the characteristic imaging findings of SPT in the pediatric age group and to establish a correlation with typical histopathological findings of the lesion.

Modelling world investment markets using threshold conditional correlation models

In this paper we propose a parsimonious regime-switching approach to model the correlations between assets, the threshold conditional correlation (TCC) model. This method allows the dynamics of the correlations to change from one state (or regime) to another as a function of observable transition variables. Our model is similar in spirit to Silvennoinen and Teräsvirta (2009) and Pelletier (2006) but with the appealing feature that it does not suffer from the course of dimensionality. In particular, estimation of the parameters of the TCC involves a simple grid search procedure. In addition, it is easy to guarantee a positive definite correlation matrix because the TCC estimator is given by the sample correlation matrix, which is positive definite by construction. The methodology is illustrated by evaluating the behaviour of international equities, govenrment bonds and major exchange rates, first separately and then jointly. We also test and allow for different parts in the correlation matrix to be governed by different transition variables. For this, we estimate a multi-threshold TCC specification. Further, we evaluate the economic performance of the TCC model against a constant conditional correlation (CCC) estimator using a Diebold-Mariano type test. We conclude that threshold correlation modelling gives rise to a significant reduction in portfolio´s variance.

Ecological Footprint Inequality across countries: the role of environment intensity, income and interaction effects

Recently, White (2007) analysed the international inequalities in Ecological Footprints per capita (EF hereafter) based on a two-factor decomposition of an index from the Atkinson family (Atkinson (1970)). Specifically, this paper evaluated the separate role of environment intensity (EF/GDP) and average income as explanatory factors for these global inequalities. However, in addition to other comments on their appeal, this decomposition suffers from the serious limitation of the omission of the role exerted by probable factorial correlation (York et al. (2005)). This paper proposes, by way of an alternative, a decomposition of a conceptually similar index like Theil’s (Theil, 1967) which, in effect, permits clear decomposition in terms of the role of both factors plus an inter-factor correlation, in line with Duro and Padilla (2006). This decomposition might, in turn, be extended to group inequality components (Shorrocks, 1980), an analysis that cannot be conducted in the case of the Atkinson indices. The proposed methodology is implemented empirically with the aim of analysing the international inequalities in EF per capita for the 1980-2007 period and, amongst other results, we find that, indeed, the interactive component explains, to a significant extent, the apparent pattern of stability observed in overall international inequalities. Key words: ecological footprint; international environmental distribution; inequality decomposition

Correlation of intra- and extraepidermal CD8 T cell numbers with development of psoriatic epidermal pathology

The development of psoriatic plaques is T cell dependent. Recently, Th17 CD4 T cells have been proposed to be the main effector cells. However, development of psoriasis is critically dependent on accumulation of epidermal T cells, among the majority express CD8. Here we show that numbers of epidermal CD8 T cells correlated with development of psoriasis in human biopsies, and that blockade of CD8 T cells by depleting antibodies inhibited development of psoriasis in the AGR xenotransplantation mouse model. In human dermis, both CD4 and CD8 T cell numbers correlated significantly with epidermal pathology, indicating a role for dermal CD4 T cells in orchestrating the development of psoriasiform changes induced by epidermis-infiltrating CD8 T cells.

Pattern of use of radiotherapy for lung cancer: a descriptive study.

BACKGROUND Lung cancer remains one of the most prevalent forms of cancer. Radiotherapy, with or without other therapeutic modalities, is an effective treatment. Our objective was to report on the use of radiotherapy for lung cancer, its variability in our region, and to compare our results with the previous study done in 2004 (VARA-I) in our region and with other published data. METHODS We reviewed the clinical records and radiotherapy treatment sheets of all patients undergoing radiotherapy for lung cancer during 2007 in the 12 public hospitals in Andalusia, an autonomous region of Spain. Data were gathered on hospital, patient type and histological type, radiotherapy treatment characteristics, and tumor stage. RESULTS 610 patients underwent initial radiotherapy. 37% of cases had stage III squamous cell lung cancer and were treated with radical therapy. 81% of patients with non-small and small cell lung cancer were treated with concomitant chemo-radiotherapy and the administered total dose was ≥60 Gy and ≥45 Gy respectively. The most common regimen for patients treated with palliative intent (44.6%) was 30 Gy. The total irradiation rate was 19.6% with significant differences among provinces (range, 8.5-25.6%; p<0.001). These differences were significantly correlated with the geographical distribution of radiation oncologists (r=0.78; p=0.02). Our results were similar to other published data and previous study VARA-I. CONCLUSIONS Our results shows no differences according to the other published data and data gathered in the study VARA-I. There is still wide variability in the application of radiotherapy for lung cancer in our setting that significantly correlates with the geographical distribution of radiation oncologists.

Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Pattern of cytokine and chemokine production by THP-1 derived macrophages in response to live or heat-killed Mycobacterium bovis bacillus Calmette-Guérin Moreau strain

Tuberculosis has great public health impact with high rates of mortality and the only prophylactic measure for it is the Mycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine. The present study evaluated the release of cytokines [interleukin (IL)-1, tumour necrosis factor and IL-6] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-1β] by THP-1 derived macrophages infected with BCG vaccine obtained by growing mycobacteria in Viscondessa de Moraes Institute medium medium (oral) or Sauton medium (intradermic) to compare the effects of live and heat-killed (HK) mycobacteria. Because BCG has been reported to lose viability during the lyophilisation process and during storage, we examined whether exposing BCG to different temperatures also triggers differences in the expression of some important cytokines and chemokines of the immune response. Interestingly, we observed that HK mycobacteria stimulated cytokine and chemokine production in a different pattern from that observed with live mycobacteria.

The EU ‘2020 Energy Initiative’: The post-Lisbon pattern of change in EU energy policy

El novembre de 2010, la Comissió Europea ha finalment donat a conèixer la seva "Energia 2020 Comunicació", un document estratègic en el marc més ampli del programa "Europa 2020". Una estratègia per al desenvolupament sostenible intel · ligent, i creixement inclusiu posa les bases d'un nou enfocament a la política d'energia a la UE. En el marc d'Europa 2020, la Iniciativa d'Energia recopila els resultats que ja s'han obtingut a través de la Estratègia de Lisboa 2000-2010, s'identifiquen les deficiències del passat i i introdueix nous objectius ambiciosos per a la UE en matèria de política energètica.

Correlation between TH1 response standard cytokines as biomarkers in patients with the delta virus in the western Brazilian Amazon

Hepatitis D virus (HDV) is endemic in the Amazon Region and its pathophysiology is the most severe among viral hepatitis. Treatment is performed with pegylated interferon and the immune response appears to be important for infection control. HDV patients were studied: untreated and polymerase chain reaction (PCR) positive (n = 9), anti-HDV positive and PCR negative (n = 8), and responders to treatment (n = 12). The cytokines, interleukin (IL)-2 (p = 0.0008) and IL-12 (p = 0.02) were differentially expressed among the groups and were also correlated (p = 0.0143). Future studies will be conducted with patients at different stages of treatment, associating the viral load with serum cytokines produced, thereby attempting to establish a prognostic indicator of the infection.

Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study.

Background Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. Methods We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Results Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98). Conclusions The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. Keywords: Endothelial dysfunction; Diabetes mellitus; Coronary microcirculation