How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS).

Una relación especial: Privatización de la seguridad, élites vulnerables y sistema político (1982-2002)

En las décadas comprendidas entre 1982 y 2002, Colombia ya se afirmaba como un Estado democrático. Sin embargo, en este período el paramilitarismo agenció uno de los más agudos niveles de violencia homicida en el país. Ante esta realidad incuestionable, surgen planteamientos que intentan explicar esta paradoja: a) Colombia no es una democracia: es un régimen terrorista que acaba con la oposición para mantener un sistema de exclusiones desde arriba; b) las instituciones colombianas han sido una víctima más de la violencia paramilitar; y c) el paramilitarismo obedece a la insurgencia de élites locales y regionales contra procesos de paz impulsados desde arriba. Las dos primeras, claramente cuestionables. La última, todavía insuficiente a la hora de identificar el papel de los tomadores de decisiones a nivel central, tanto en el Estado como en el sistema político, en el despliegue y auge del fenómeno paramilitar.Este artículo evalúa estas tres afirmaciones y analiza, con base en documentos oficiales e informes de prensa de la época, los alcances del paramilitarismo en las décadas comprendidas entre 1982 y 2002, al tenor del papel desempeñado por la democracia colombiana y sus instituciones, pues –alcontrario del discurso oficial de los gobiernos, quienes por más de treinta años han afirmado haber sufrido la penetración y agresión del paramilitarismo de la mano de “manzanas podridas” o “casos aislados”– el fenómeno paramilitar en Colombia durante el período estudiado disfrutó de un estatus especial agenciado públicamente por políticos centristas, prosaicos y conciliadores apuntalados en las presiones de sectoresclave del sistema político y de las élites vulnerables del país.

Rearrangement of the urban space in the sector of Saint Victorino and Saint Ines (Bogota) in relation with the dynamics of informality and marginality (1948-2010)

The present article analyze the urban transformations happened in the sector of Saint Victorino and Saint Ines in the city of Bogota D.C. between 1948 and 2010, making use of the "Genealogical Methodology" during the process of inquiry that allow to contrast the visions that are usually accepted of "progress" and "urban renovation" in the urban market context by the existence of a informal economic and a population in conditions of marginality that configures a good part of the "popular urban culture" of the Bogota in the 20th and 21st century. This vision permit to observe from various perspectives the changes that happened in this sector of the city, the impacts of the history facts occurred en this time period and, in special, the real effects of a rearrangement urban process that began in 1998 and has been prolonged to date, which has left a significant mark about the urban and social physiognomy of the place.

Patrones de cambio en el paisaje urbano del sector patrimonial Quinta Camacho por cambios en el uso del suelo diferentes al residencial. Periodo: 2000-2015

El legado cultural, producto de las tradiciones de cada grupo poblacional, queda plasmado en el territorio por medio de objetos que hacen parte del Patrimonio Construido. Este, debe ser perdurable en el tiempo, manteniendo viva su esencia al evocar una época o hecho particular. Para dicha preservación, las sociedades han desarrollado un gran arsenal de herramientas, pero, ¿Es realmente adecuada su conservación? ¿El Patrimonio Construido realmente cumple una función acorde al territorio donde se ubica? Frente a estos dos grandes cuestionamientos se apela a la gestión y el desarrollo urbano como la disciplina idónea para intervenir el patrimonio, ya que genera una aproximación multidisciplinar en donde la gestión y la toma de decisiones concernientes al patrimonio se dan de forma eficiente, logrando conservar un legado del pasado a la vez que cumplir una función en el presente acorde a las dinámicas cambiantes de un asentamiento humano.

Effects of Spruce Budworm (Choristoneura fumiferana (Clem.)) Outbreaks on Boreal Mixed-Wood Bird Communities

This study examined the influence of a spruce budworm (Choristoneura fumiferana (Clem.)) outbreak on a boreal mixed-wood bird community in forest stands ranging in age from 0 to 223 yr. We asked if (1) patterns of species response were consistent with the existence of spruce budworm specialists, i.e., species that respond in a stronger quantitative or qualitative way than other species; (2) the superabundance of food made it possible for species to expand their habitat use in age classes that were normally less used; and (3) the response to budworm was limited to specialists or was it more widespread. Results here indicated that three species, specifically the Bay-breasted Warbler (Dendroica castanea), Tennessee Warbler (Vermivora peregrina), and Cape May Warbler (Dendroica tigrina), had a larger numerical response to the budworm outbreak. They responded with increases in density of up to tenfold over 4 or 5 yr. No other species responded with more than a twofold increase in the same time period. These species also showed a functional response by breeding more frequently in young stands aged 1–21 yr and intermediate stands aged 22–36 yr as budworm numbers increased. Our data also suggested that many species profited to a lesser extent from budworm outbreaks, but that this effect may be too subtle to detect in most studies. We found evidence of a positive numerical effect in at least 18 additional species in one or two stand-age categories but never in all three for any one species. Given the numerical response in many species and the potential influence of budworm on bird populations because of the vast extent of outbreaks, we believe that the population cycle of spruce budworm should be considered in any evaluation of population trends in eastern boreal birds.

How robust are observed and simulated precipitation responses to tropical ocean warming?

Robust responses and links between the tropical energy and water cycles are investigated using multiple datasets and climate models over the period 1979-2006. Atmospheric moisture and net radiative cooling provide powerful constraints upon future changes in precipitation. While moisture amount is robustly linked with surface temperature, the response of atmospheric net radiative cooling, derived from satellite data, is less coherent. Precipitation trends and relationships with surface temperature are highly sensitive to the data product and the time-period considered. Data from the Special Sensor Microwave Imager (SSM/I) produces the strongest trends in precipitation and response to warming of all the datasets considered. The tendency for moist regions to become wetter while dry regions become drier in response to warming is captured by both observations and models. Citation: John, V. O., R. P. Allan, and B. J. Soden (2009), How robust are observed and simulated precipitation responses to tropical ocean warming?

Over-parameterised, uncertain 'mathematical marionettes' - How can we best use catchment water quality models? An example of an 80-year catchment-scale nutrient balance

The Integrated Catchment Model of Nitrogen (INCA-N) was applied to the River Lambourn, a Chalk river-system in southern England. The model's abilities to simulate the long-term trend and seasonal patterns in observed stream water nitrate concentrations from 1920 to 2003 were tested. This is the first time a semi-distributed, daily time-step model has been applied to simulate such a long time period and then used to calculate detailed catchment nutrient budgets which span the conversion of pasture to arable during the late 1930s and 1940s. Thus, this work goes beyond source apportionment and looks to demonstrate how such simulations can be used to assess the state of the catchment and develop an understanding of system behaviour. The mass-balance results from 1921, 1922, 1991, 2001 and 2002 are presented and those for 1991 are compared to other modelled and literature values of loads associated with nitrogen soil processes and export. The variations highlighted the problem of comparing modelled fluxes with point measurements but proved useful for identifying the most poorly understood inputs and processes thereby providing an assessment of input data and model structural uncertainty. The modelled terrestrial and instream mass-balances also highlight the importance of the hydrological conditions in pollutant transport. Between 1922 and 2002, increased inputs of nitrogen from fertiliser, livestock and deposition have altered the nitrogen balance with a shift from possible reduction in soil fertility but little environmental impact in 1922, to a situation of nitrogen accumulation in the soil, groundwater and instream biota in 2002. In 1922 and 2002 it was estimated that approximately 2 and 18 kg N ha(-1) yr(-1) respectively were exported from the land to the stream. The utility of the approach and further considerations for the best use of models are discussed. (C) 2008 Elsevier B.V. All rights reserved.

Earthworm induced mineral weathering: preliminary results

The role of earthworms in mineral weathering was investigated. The minerals anorthite, biotite, olivine, smectite and kaolinite were mixed with a sterilized manure substrate. Two treatments were used: minerals with earthworms and minerals without earthworms. The earthworms were established in mesocosms and left to process the substrates for 1, 2, 4 and 6 months. Four sacrificial replicates were used per time period. Changes in mineralogy were analysed using X-ray diffraction. Weathering of anorthite, biotite, smectite and kaolinite appears to be accelerated by the earthworms. There was evidence for the transformation of smectite to illite and the formation of a new mineral phase from kaolinite. Olivine appears not to be weathered by earthworms. Different minerals also appear to weather at different rates. (c) 2007 Elsevier Masson SAS. All rights reserved.

Does reactive surface area depend on grain size? Results from pH 3, 25 circle C far-from-equilibrium flow-through dissolution experiments on anorthite and biotite

Laboratory determined mineral weathering rates need to be normalised to allow their extrapolation to natural systems. The principle normalisation terms used in the literature are mass, and geometric- and BET specific surface area (SSA). The purpose of this study was to determine how dissolution rates normalised to these terms vary with grain size. Different size fractions of anorthite and biotite ranging from 180-150 to 20-10 mu m were dissolved in pH 3, HCl at 25 degrees C in flow through reactors under far from equilibrium conditions. Steady state dissolution rates after 5376 h (anorthite) and 4992 h (biotite) were calculated from Si concentrations and were normalised to initial- and final- mass and geometric-, geometric edge- (biotite), and BET SSA. For anorthite, rates normalised to initial- and final-BET SSA ranged from 0.33 to 2.77 X 10(-10) mol(feldspar) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 5.74 to 8.88 X 10(-10) mol(feldspar) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.11 to 1.65 mol(feldspar) g(-1) s(-1). For biotite, rates normalised to initial- and final-BET SSA ranged from 1.02 to 2.03 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 3.26 to 16.21 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric edge SSA ranged from 59.46 to 111.32 x 10(-12) mol(biotite) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.81 to 6.93 X 10(-12) mol(biotite) g(-1) s(-1). For all normalising terms rates varied significantly (p <= 0.05) with grain size. The normalising terms which gave least variation in dissolution rate between grain sizes for anorthite were initial BET SSA and initial- and final-geometric SSA. This is consistent with: (1) dissolution being dominated by the slower dissolving but area dominant non-etched surfaces of the grains and, (2) the walls of etch pits and other dissolution features being relatively unreactive. These steady state normalised dissolution rates are likely to be constant with time. Normalisation to final BET SSA did not give constant ratios across grain size due to a non-uniform distribution of dissolution features. After dissolution coarser grains had a greater density of dissolution features with BET-measurable but unreactive wall surface area than the finer grains. The normalising term which gave the least variation in dissolution rates between grain sizes for biotite was initial BET SSA. Initial- and final-geometric edge SSA and final BET SSA gave the next least varied rates. The basal surfaces dissolved sufficiently rapidly to influence bulk dissolution rate and prevent geometric edge SSA normalised dissolution rates showing the least variation. Simple modelling indicated that biotite grain edges dissolved 71-132 times faster than basal surfaces. In this experiment, initial BET SSA best integrated the different areas and reactivities of the edge and basal surfaces of biotite. Steady state dissolution rates are likely to vary with time as dissolution alters the ratio of edge to basal surface area. Therefore they would be more properly termed pseudo-steady state rates, only appearing constant because the time period over which they were measured (1512 h) was less than the time period over wich they would change significantly. (c) 2006 Elsevier Inc. All rights reserved.

Results from the Covered Catchment Experiment at Gårdsjön, Sweden, after ten years of clean precipitation treatment

The Covered Catchment Experiment at Gordsjon is a large scale forest ecosystem manipulation, where acid precipitation was intercepted by a 7000 m(2) plastic roof and replaced by 'clean precipitation' sprinkled below the roof for ten years between 1991 and 2001. The treatment resulted in a strong positive response of runoff quality. The runoff sulphate, inorganic aluminium and base cations decreased, while there was a strong increase in runoff ANC and a moderate increase in pH. The runoff continued to improve over the whole duration of the experiment. The achieved quality was, however, after ten years still considerably worse than estimated pre-industrial runoff at the site. Stable isotopes of sulphur were analysed to study the soil sulphur cycling. At the initial years of the experiment, the desorption of SO4 from the mineral soil appeared to control the runoff SO4 concentration. However, as the experiment proceeded, there was growing evidence that net mineralisation of soil organic sulphur in the humus layer was an additional source of SO4 in runoff. This might provide a challenge to current acidification models. The experiment convincingly demonstrated on a catchment scale, that reduction in acid deposition causes an immediate improvement of surface water quality even at heavily acidified sites. The improvement of the runoff appeared to be largely a result of cation exchange processes in the soil due to decreasing concentrations of the soil solution, while any potential change in soil base saturation seemed to be less important for the runoff chemistry over the short time period of one decade. These findings should be considered when interpreting and extrapolating regional trends in surface water chemistry to the terrestrial parts of ecosystems.

Over-parameterised, uncertain 'mathematical marionettes' - How can we best use catchment water quality models? An example of an 80-year catchment-scale nutrient balance

The Integrated Catchment Model of Nitrogen (INCA-N) was applied to the River Lambourn, a Chalk river-system in southern England. The model's abilities to simulate the long-term trend and seasonal patterns in observed stream water nitrate concentrations from 1920 to 2003 were tested. This is the first time a semi-distributed, daily time-step model has been applied to simulate such a long time period and then used to calculate detailed catchment nutrient budgets which span the conversion of pasture to arable during the late 1930s and 1940s. Thus, this work goes beyond source apportionment and looks to demonstrate how such simulations can be used to assess the state of the catchment and develop an understanding of system behaviour. The mass-balance results from 1921, 1922, 1991, 2001 and 2002 are presented and those for 1991 are compared to other modelled and literature values of loads associated with nitrogen soil processes and export. The variations highlighted the problem of comparing modelled fluxes with point measurements but proved useful for identifying the most poorly understood inputs and processes thereby providing an assessment of input data and model structural uncertainty. The modelled terrestrial and instream mass-balances also highlight the importance of the hydrological conditions in pollutant transport. Between 1922 and 2002, increased inputs of nitrogen from fertiliser, livestock and deposition have altered the nitrogen balance with a shift from possible reduction in soil fertility but little environmental impact in 1922, to a situation of nitrogen accumulation in the soil, groundwater and instream biota in 2002. In 1922 and 2002 it was estimated that approximately 2 and 18 kg N ha(-1) yr(-1) respectively were exported from the land to the stream. The utility of the approach and further considerations for the best use of models are discussed. (C) 2008 Elsevier B.V. All rights reserved.

The climate sensitivity and its components diagnosed from Earth Radiation Budget data

One of the major uncertainties in the ability to predict future climate change, and hence its impacts, is the lack of knowledge of the earth's climate sensitivity. Here, data are combined from the 1985-96 Earth Radiation Budget Experiment (ERBE) with surface temperature change information and estimates of radiative forcing to diagnose the climate sensitivity. Importantly, the estimate is completely independent of climate model results. A climate feedback parameter of 2.3 +/- 1.4 W m(-2) K-1 is found. This corresponds to a 1.0-4.1-K range for the equilibrium warming due to a doubling of carbon dioxide (assuming Gaussian errors in observable parameters, which is approximately equivalent to a uniform "prior" in feedback parameter). The uncertainty range is due to a combination of the short time period for the analysis as well as uncertainties in the surface temperature time series and radiative forcing time series, mostly the former. Radiative forcings may not all be fully accounted for; however, all argument is presented that the estimate of climate sensitivity is still likely to be representative of longer-term climate change. The methodology can be used to 1) retrieve shortwave and longwave components of climate feedback and 2) suggest clear-sky and cloud feedback terms. There is preliminary evidence of a neutral or even negative longwave feedback in the observations, suggesting that current climate models may not be representing some processes correctly if they give a net positive longwave feedback.

TIGGE: Comparison of the prediction of northern hemisphere extratropical cyclones by different ensemble prediction systems

The Observing System Research and Predictability Experiment (THORPEX) Interactive Grand Global Ensemble (TIGGE) is a World Weather Research Programme project. One of its main objectives is to enhance collaboration on the development of ensemble prediction between operational centers and universities by increasing the availability of ensemble prediction system (EPS) data for research. This study analyzes the prediction of Northern Hemisphere extratropical cyclones by nine different EPSs archived as part of the TIGGE project for the 6-month time period of 1 February 2008–31 July 2008, which included a sample of 774 cyclones. An objective feature tracking method has been used to identify and track the cyclones along the forecast trajectories. Forecast verification statistics have then been produced [using the European Centre for Medium-Range Weather Forecasts (ECMWF) operational analysis as the truth] for cyclone position, intensity, and propagation speed, showing large differences between the different EPSs. The results show that the ECMWF ensemble mean and control have the highest level of skill for all cyclone properties. The Japanese Meteorological Administration (JMA), the National Centers for Environmental Prediction (NCEP), the Met Office (UKMO), and the Canadian Meteorological Centre (CMC) have 1 day less skill for the position of cyclones throughout the forecast range. The relative performance of the different EPSs remains the same for cyclone intensity except for NCEP, which has larger errors than for position. NCEP, the Centro de Previsão de Tempo e Estudos Climáticos (CPTEC), and the Australian Bureau of Meteorology (BoM) all have faster intensity error growth in the earlier part of the forecast. They are also very underdispersive and significantly underpredict intensities, perhaps due to the comparatively low spatial resolutions of these EPSs not being able to accurately model the tilted structure essential to cyclone growth and decay. There is very little difference between the levels of skill of the ensemble mean and control for cyclone position, but the ensemble mean provides an advantage over the control for all EPSs except CPTEC in cyclone intensity and there is an advantage for propagation speed for all EPSs. ECMWF and JMA have an excellent spread–skill relationship for cyclone position. The EPSs are all much more underdispersive for cyclone intensity and propagation speed than for position, with ECMWF and CMC performing best for intensity and CMC performing best for propagation speed. ECMWF is the only EPS to consistently overpredict cyclone intensity, although the bias is small. BoM, NCEP, UKMO, and CPTEC significantly underpredict intensity and, interestingly, all the EPSs underpredict the propagation speed, that is, the cyclones move too slowly on average in all EPSs.

Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitro

Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess oestrogenic activity in assays using the oestrogen-responsive MCF7 human breast cancer cell line. At 3 000 000-fold molar excess, they were able to partially displace [H-3]oestradiol from recombinant human oestrogen receptors ER alpha and ER beta, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 x 10(-5) to 5 x 10(-4) M, they were able to increase the expression of a stably integrated oestrogen-responsive reporter gene (ERE-CAT) and of the endogenous oestrogen-responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10(-8) M 17 beta-oestradiol. They increased the proliferation of oestrogen-dependent MCF7 cells over 7 days, which could be inhibited by the antioestrogen fulvestrant, suggesting an ER-mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10(-8) M 17 beta-oestradiol, given a longer time period of 35 days the extent of proliferation with 10(-4) M benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10(-8) M 17 beta-oestradiol over 14 days. This demonstrates that benzyl salicylate, benzyl benzoate and butylphenylmethylpropional are further chemical components of cosmetic products which give oestrogenic responses in a human breast cancer cell line in culture. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues. Copyright (C) 2009 John Wiley & Sons, Ltd.

Oocyte-mediated suppression of follicle-stimulating hormone- and insulin-like growth factor-induced secretion of steroids and inhibin-related proteins by bovine granulosa cells in vitro: Possible role of transforming growth factor alpha

The objective was to investigate the potential role of the oocyte in modulating proliferation and basal, FSH-induced and insulin-like growth factor (IGF)-induced secretion of inhibin A (inh A), activin A (act A), follistatin (FS), estradiol (E-2), and progesterone (P-4) by mural bovine granulosa cells. Cells from 4- to 6-mm follicles were cultured in serum-free medium containing insulin and androstenedione, and the effects of ovine FSH and IGF analogue (LR3-IGF-1) were tested alone and in the presence of denuded bovine oocytes (2, 8, or 20 per well). Medium was changed every 48 h, cultures were terminated after 144 h, and viable cell number was determined. Results are based on combined data from four independent cultures and are presented for the last time period only when responses were maximal. Both FSH and IGF increased (P < 0.001) secretion of inh A, act A, FS, E-2, and P-4 and raised cell number. In the absence of FSH or IGF, coculture with oocytes had no effect on any of the measured hormones, although cell number was increased up to 1.8-fold (P < 0.0001). Addition of oocytes to FSH-stimulated cells dose-dependently suppressed (P < 0.0001) inh A (6-fold maximum suppression), act A (5.5-fold), FS (3.6-fold), E-2 (4.6-fold), and P-4 (2.4-fold), with suppression increasing with FSH dose. Likewise, oocytes suppressed (P < 0.001) IGF-induced secretion of inh A, act A, FS, and E-2 (P < 0.05) but enhanced IGF-induced P-4 secretion (1.7-fold; P < 0.05). Given the similarity of these oocyte-mediated actions to those we observed previously following epidermal growth factor (EGF) treatment, we used immunocytochemistry to determine whether bovine oocytes express EGF or transforming growth factor (TGF) alpha. Intense staining with TGFalpha antibody (but not with EGF antibody) was detected in oocytes both before and after coculture. Experiments involving addition of TGFalpha to granulosa cells confirmed that the peptide mimicked the effects of oocytes on cell proliferation and on FSH- and IGF-induced hormone secretion. These experiments indicate that bovine oocytes secrete a factor(s) capable of modulating granulosa cell proliferation and responsiveness to FSH and IGF in terms of steroidogenesis and production of inhibin-related peptides, bovine oocytes express TGFalpha but not EGF, and TGFalpha is a prime candidate for mediating the actions of oocytes on bovine granulosa cells.