Patterns and trends in esophageal cancer mortality and incidence in Europe (1980-2011) and predictions to 2015

BACKGROUND: Over the last few decades, esophageal cancer incidence and mortality trends varied substantially across Europe, with important differences between sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). PATIENTS AND METHODS: To monitor recent esophageal cancer mortality trends and to compute short-term predictions in the European Union (EU) and selected European countries, we analyzed data provided by the World Health Organization (WHO) for 1980-2011. We also analyzed incidence trends and relative weights of ESCC and EAC across Europe using data from Cancer Incidence in Five Continents. RESULTS: Long-term decreasing trends were observed for male esophageal cancer mortality in several southern and western European countries, whereas in central Europe mortality increased until the mid-1990s and started to stabilize or decline over the last years. In some eastern and northern countries, the rates were still increasing. Mortality among European women remained comparatively low and showed stable or decreasing trends in most countries. Between 2000-2004 and 2005-2009, esophageal cancer mortality declined by 7% (from 5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU women. Predictions to 2015 show persistent declines in mortality rates for men in the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000 men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern Europe, EAC is now the predominant histological type among men, while for European women ESCC is more common and corresponding rates are still increasing in several countries. CONCLUSION(S): The observed trends reflect the variations in alcohol drinking, tobacco smoking and overweight across European countries.

Extent and Patterns of MGMT Promoter Methylation in Glioblastoma- and Respective Glioblastoma-Derived Spheres.

PURPOSE: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. EXPERIMENTAL DESIGN: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), cultured under stem cell conditions, were analyzed for the degree and pattern of MGMT promoter methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin status, and respective effects on MGMT expression and MGMT activity. RESULTS: In glioblastoma, MGMT-methylated alleles ranged from 10% to 90%. In contrast, methylated alleles were highly enriched (100% of clones) in respective GS, even when 2 MGMT alleles were present, with 1 exception (<50%). The CpG methylation patterns were characteristic for each glioblastoma exhibiting 25% to 90% methylated CpGs of 28 sites interrogated. Furthermore, MGMT promoter methylation was associated with a nonpermissive chromatin status in accordance with very low MGMT transcript levels and undetectable MGMT activity. CONCLUSIONS: In MGMT-methylated glioblastoma, MGMT promoter methylation is highly enriched in GS that supposedly comprise glioma-initiating cells. Thus, even a low percentage of MGMT methylation measured in a glioblastoma sample may be relevant and predict benefit from an alkylating agent therapy. Clin Cancer Res; 17(2); 255-66. ©2010 AACR.

Alcohol-attributable injuries in admissions to a swiss emergency room--an analysis of the link between volume of drinking, drinking patterns, and preattendance drinking.

BACKGROUND: An association between alcohol consumption and injury is clearly established from volume of drinking, heavy episodic drinking (HED), and consumption before injury. Little is known, however, about how their interaction raises risk of injury and what combination of factors carries the highest risk. This study explores which of 11 specified groups of drinkers (a) are at high risk and (b) contribute most to alcohol-attributable injuries. METHODS: In all, 8,736 patients, of whom 5,077 were injured, admitted to the surgical ward of the emergency department of Lausanne University Hospital between January 1, 2003, and June 30, 2004, were screened for alcohol use. Eleven groups were constructed on the basis of usual patterns of intake and preattendance drinking. Odds ratios (ORs) comparing injured and noninjured were derived, and alcohol-attributable fractions of injuries were calculated from ORs and prevalence of exposure groups. RESULTS: Risk of injury increased with volume of drinking, HED, and preattendance drinking. For both sexes, the highest risk was associated with low intake, HED, and 4 (women), 5 (men), or more drinks before injury. At the same level of preattendance drinking, high-volume drinkers were at lower risk than low-volume drinkers. In women, the group of low-risk non-HED drinkers taking fewer than 4 drinks suffered 47.5% of the alcohol-attributable injuries in contrast to only 20.4% for men. Low-volume male drinkers with HED had more alcohol-attributable injuries than that of low-volume female drinkers with HED (46.9% vs 23.2%). CONCLUSIONS: Although all groups of drinkers are at increased risk of alcohol-related injury, those who usually drink little but on occasion heavily are at particular risk. The lower risk of chronic heavy drinkers may be due to higher tolerance of alcohol. Prevention should thus target heavy-drinking occasions. Low-volume drinking women without HED and with only little preattendance drinking experienced a high proportion of injuries; such women would be well advised to drink very little or to take other special precautions in risky circumstances.

Patterns of positive selection in seven ant genomes.

The evolution of ants is marked by remarkable adaptations that allowed the development of very complex social systems. To identify how ant-specific adaptations are associated with patterns of molecular evolution, we searched for signs of positive selection on amino-acid changes in proteins. We identified 24 functional categories of genes which were enriched for positively selected genes in the ant lineage. We also reanalyzed genome-wide data sets in bees and flies with the same methodology to check whether positive selection was specific to ants or also present in other insects. Notably, genes implicated in immunity were enriched for positively selected genes in the three lineages, ruling out the hypothesis that the evolution of hygienic behaviors in social insects caused a major relaxation of selective pressure on immune genes. Our scan also indicated that genes implicated in neurogenesis and olfaction started to undergo increased positive selection before the evolution of sociality in Hymenoptera. Finally, the comparison between these three lineages allowed us to pinpoint molecular evolution patterns that were specific to the ant lineage. In particular, there was ant-specific recurrent positive selection on genes with mitochondrial functions, suggesting that mitochondrial activity was improved during the evolution of this lineage. This might have been an important step toward the evolution of extreme lifespan that is a hallmark of ants.

Regional integration and specialisation patterns in Spain

The aim of this paper is to analyse how economic integration in Europe has affected industrial geographical concentration in Spain and explain what the driving forces behind industry location are. Firstly, we construct regional specialisation and geographical concentration indices for Spanish 50 provinces and 30 industrial sectors in 1979, 1986 and 1992. Secondly, we carry out an econometric analysis of the determinants of geographical concentration of industries. Our main conclusion is that there is no evidence of increasing specialisation in Spain between 1979 and 1992 and that the most important determinant of Spain¿s economic geography is scale economies. Furthermore, traditional trade theory has no effects in explaining the pattern of industrial concentration

Radiotherapy suppresses angiogenesis in mice through TGF-betaRI/ALK5-dependent inhibition of endothelial cell sprouting.

BACKGROUND: Radiotherapy is widely used to treat cancer. While rapidly dividing cancer cells are naturally considered the main target of radiotherapy, emerging evidence indicates that radiotherapy also affects endothelial cell functions, and possibly also their angiogenic capacity. In spite of its clinical relevance, such putative anti-angiogenic effect of radiotherapy has not been thoroughly characterized. We have investigated the effect of ionizing radiation on angiogenesis using in vivo, ex vivo and in vitro experimental models in combination with genetic and pharmacological interventions. PRINCIPAL FINDINGS: Here we show that high doses ionizing radiation locally suppressed VEGF- and FGF-2-induced Matrigel plug angiogenesis in mice in vivo and prevented endothelial cell sprouting from mouse aortic rings following in vivo or ex vivo irradiation. Quiescent human endothelial cells exposed to ionizing radiation in vitro resisted apoptosis, demonstrated reduced sprouting, migration and proliferation capacities, showed enhanced adhesion to matrix proteins, and underwent premature senescence. Irradiation induced the expression of P53 and P21 proteins in endothelial cells, but p53 or p21 deficiency and P21 silencing did not prevent radiation-induced inhibition of sprouting or proliferation. Radiation induced Smad-2 phosphorylation in skin in vivo and in endothelial cells in vitro. Inhibition of the TGF-beta type I receptor ALK5 rescued deficient endothelial cell sprouting and migration but not proliferation in vitro and restored defective Matrigel plug angiogenesis in irradiated mice in vivo. ALK5 inhibition, however, did not rescue deficient proliferation. Notch signaling, known to hinder angiogenesis, was activated by radiation but its inhibition, alone or in combination with ALK5 inhibition, did not rescue suppressed proliferation. CONCLUSIONS: These results demonstrate that irradiation of quiescent endothelial cells suppresses subsequent angiogenesis and that ALK5 is a critical mediator of this suppression. These results extend our understanding of radiotherapy-induced endothelial dysfunctions, relevant to both therapeutic and unwanted effects of radiotherapy.

Socioeconomic determinants of dietary patterns in low- and middle-income countries : a systematic review

BACKGROUND: In high-income countries, high socioeconomic status (SES) is generally associated with a healthier diet, but whether social differences in dietary intake are also present in low- and middle-income countries (LMICs) remains to be established. OBJECTIVE: We performed a systematic review of studies that assessed the relation between SES and dietary intake in LMICs. DESIGN: We carried out a systematic review of cohort and cross-sectional studies in adults in LMICs and published between 1996 and 2013. We assessed associations between markers of SES or urban and rural settings and dietary intake. RESULTS: A total of 33 studies from 17 LMICs were included (5 low-income countries and 12 middle-income countries; 31 cross-sectional and 2 longitudinal studies). A majority of studies were conducted in Brazil (8), China (6), and Iran (4). High SES or living in urban areas was associated with higher intakes of calories; protein; total fat; cholesterol; polyunsaturated, saturated, and monounsaturated fatty acids; iron; and vitamins A and C and with lower intakes of carbohydrates and fiber. High SES was also associated with higher fruit and/or vegetable consumption, diet quality, and diversity. Although very few studies were performed in low-income countries, similar patterns were generally observed in both LMICs except for fruit intake, which was lower in urban than in rural areas in low-income countries. CONCLUSIONS: In LMICs, high SES or living in urban areas is associated with overall healthier dietary patterns. However, it is also related to higher energy, cholesterol, and saturated fat intakes. Social inequalities in dietary intake should be considered in the prevention and control of noncommunicable diseases in LMICs.

Regional integration and specialisation patterns in Spain

The aim of this paper is to analyse how economic integration in Europe has affected industrial geographical concentration in Spain and explain what the driving forces behind industry location are. Firstly, we construct regional specialisation and geographical concentration indices for Spanish 50 provinces and 30 industrial sectors in 1979, 1986 and 1992. Secondly, we carry out an econometric analysis of the determinants of geographical concentration of industries. Our main conclusion is that there is no evidence of increasing specialisation in Spain between 1979 and 1992 and that the most important determinant of Spain¿s economic geography is scale economies. Furthermore, traditional trade theory has no effects in explaining the pattern of industrial concentration

Adult-type rhabdomyosarcoma: analysis of 57 cases with clinicopathologic description, identification of 3 morphologic patterns and prognosis.

Adult-type rhabdomyosarcoma (RMS) has been classically defined as a pleomorphic sarcoma with desmin expression occurring in adult patients. To reevaluate this entity, we analyzed a series of 57 cases using immunohistochemistry for desmin, myogenin, alpha smooth muscle actin, h-caldesmon, pankeratin AE1/AE3, epithelial membrane antigen (EMA), S100 protein, CD34, MDM2, and CDK4. In this series, there were 36 men and 21 women aged from 22 to 87 years (median: 59). Tumors were mainly located in the lower limbs (27 cases), trunk wall (15 cases), and upper limbs (10 cases). Most tumors were deeply located (51/54) with a size from 1 to 30 cm (median: 8 cm). Cases were classified in 3 histologic categories: spindle cell RMS (25 cases), pleomorphic RMS (16 cases), and mixed type (16 cases). Forty-one tumors were grade 3 and 16 grade 2. Immunohistochemistry showed that every case was positive for desmin and myogenin. Alpha smooth muscle actin was positive in 21%, pankeratin AE1/AE3 in 20%, and CD34 in 13.2%. Treatment modalities and follow-up were available in 46 cases. Median follow-up was 60.9 months. Eight patients developed a local recurrence and 16 a distant metastasis with a 5-year overall survival rate of 52.6% and a 5-year metastasis-free survival of 62.9%. The only predictive factor for metastasis was histologic grade. In conclusion, adult-type RMS is a rare sarcoma occurring mainly in the extremities and trunk wall with 2 main histologic patterns, spindle cell, and pleomorphic patterns, which represent the end of the spectrum of a single entity.

Patterns of extraocular muscle weakness in vasculopathic pupil-sparing, incomplete third nerve palsy.

OBJECTIVE: To determine the pattern of extraocular muscle (EOM) paresis in incomplete vasculopathic third nerve palsies (3NP) that have normal pupillary function. METHODS: A retrospective study in a private practice and academic neuro-ophthalmic practice. Patients diagnosed with vasculopathic 3NP within 4 weeks of symptom onset were identified. The chart of each patient was reviewed to determine pupillary function and the pattern and degree of EOM and levator palpebrae paresis at the time of presentation. RESULTS: Of 55 patients with vasculopathic 3NP, 42 (76%) had normal pupillary function. Of these 42, 23 (55%) demonstrated an incomplete EOM palsy, defined as partially reduced ductions affecting all third nerve-innervated EOMs and levator (diffuse pattern) or partially reduced ductions that involved only some third nerve-innervated EOMs and levator (focal pattern). Twenty (87%) of these 23 patients showed a diffuse pattern of paresis; only three (13%) showed a focal pattern of paresis, one that affected only the superior rectus and levator muscles (superior division weakness). CONCLUSIONS: Based on our series, most patients with EOM/levator involvement in pupil-sparing, incomplete 3NP of vasculopathic origin have a diffuse pattern of paresis. In contrast, our review of the literature suggests that pupil-sparing 3NP of aneurysmal origin usually have a focal pattern of paresis. We propose that distinguishing these two patterns of EOM paresis may be helpful in differentiating between vasculopathic and aneurysmal 3NP. Future studies will be needed to confirm the clinical utility of this hypothesis.

Patterns of calcium-binding proteins in human inferior colliculus: identification of subdivisions and evidence for putative parallel systems.

The subdivisions of human inferior colliculus are currently based on Golgi and Nissl-stained preparations. We have investigated the distribution of calcium-binding protein immunoreactivity in the human inferior colliculus and found complementary or mutually exclusive localisations of parvalbumin versus calbindin D-28k and calretinin staining. The central nucleus of the inferior colliculus but not the surrounding regions contained parvalbumin-positive neuronal somata and fibres. Calbindin-positive neurons and fibres were concentrated in the dorsal aspect of the central nucleus and in structures surrounding it: the dorsal cortex, the lateral lemniscus, the ventrolateral nucleus, and the intercollicular region. In the dorsal cortex, labelling of calbindin and calretinin revealed four distinct layers.Thus, calcium-binding protein reactivity reveals in the human inferior colliculus distinct neuronal populations that are anatomically segregated. The different calcium-binding protein-defined subdivisions may belong to parallel auditory pathways that were previously demonstrated in non-human primates, and they may constitute a first indication of parallel processing in human subcortical auditory structures.

Spatial patterns of preconsolidation pressure and soil moisture along transects in two directions under coffee

Information on the spatial structure of soil physical and structural properties is needed to evaluate the soil quality. The purpose of this study was to investigate the spatial behavior of preconsolidation pressure and soil moisture in six transects, three selected along and three across coffee rows, at three different sites under different tillage management systems. The study was carried out on a farm, in Patrocinio, state of Minas Gerais, in the Southeast of Brazil (18 º 59 ' 15 '' S; 46 º 56 ' 47 '' W; 934 m asl). The soil type is a typic dystrophic Red Latosol (Acrustox) and consists of 780 g kg-1 clay; 110 g kg-1 silt and 110 g kg-1 sand, with an average slope of 3 %. Undisturbed soil cores were sampled at a depth of 0.10-0.13 m, at three different points within the coffee plantation: (a) from under the wheel track, where equipment used in farm operations passes; (b) in - between tracks and (c) under the coffee canopy. Six linear transects were established in the experimental area: three transects along and three across the coffee rows. This way, 161 samples were collected in the transect across the coffee rows, from the three locations, while 117 samples were collected in the direction along the row. The shortest sampling distance in the transect across the row was 4 m, and 0.5 m for the transect along the row. No clear patterns of the preconsolidation pressure values were observed in the 200 m transect. The results of the semivariograms for both variables indicated a high nugget value and short range for the studied parameters of all transects. A cyclic pattern of the parameters was observed for the across-rows transect. An inverse relationship between preconsolidation pressure and soil moisture was clearly observed in the samples from under the track, in both directions.

Dynamics of turing patterns under spatiotemporal forcing

We study, both theoretically and experimentally, the dynamical response of Turing patterns to a spatiotemporal forcing in the form of a traveling-wave modulation of a control parameter. We show that from strictly spatial resonance, it is possible to induce new, generic dynamical behaviors, including temporally modulated traveling waves and localized traveling solitonlike solutions. The latter make contact with the soliton solutions of Coullet [Phys. Rev. Lett. 56, 724 (1986)] and generalize them. The stability diagram for the different propagating modes in the Lengyel-Epstein model is determined numerically. Direct observations of the predicted solutions in experiments carried out with light modulations in the photosensitive chlorine dioxide-iodine-malonic acid reaction are also reported.