Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

IMPORTANCE High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. DESIGN, SETTING, AND PARTICIPANTS The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. INTERVENTIONS HSCT vs intravenous pulse cyclophosphamide. MAIN OUTCOMES AND MEASURES The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. RESULTS A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. CONCLUSIONS AND RELEVANCE Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54371254.

Compound specific stable isotopes, BIT, pollen and spores of Miocene to Pliocene sediments of ODP Hole 175-1085A

Pollen and stable carbon (d13C) and hydrogen (dD) isotope ratios of terrestrial plant wax from the South Atlantic sediment core, ODP Site 1085, is used to reconstruct Miocene to Pliocene changes of vegetation and rainfall regime of western southern Africa. Our results reveal changes in the relative amount of precipitation and indicate a shift of the main moisture source from the Atlantic to the Indian Ocean during the onset of a major aridification 8 Ma ago. We emphasise the importance of declining precipitation during the expansion of C4 and CAM (mainly succulent) vegetation in South Africa. We suggest that the C4 plant expansion resulted from an increased equator-pole temperature gradient caused by the initiation of strong Atlantic Meridional Overturning Circulation following the shoaling of the Central American Seaway during the Late Miocene.

Palynology and radiocarbon dating on sediment profile PG1756 from Lake Billyakh, NE Siberia, Russia

In this study a radiocarbon-dated pollen record from Lake Billyakh (65°17'N, 126°47'E; 340 m a.s.l.) in the Verkhoyansk Mountains was used to reconstruct vegetation and climate change since about 15 kyr BP (1 kyr=1000 cal. yr). The pollen record and pollen-based biome reconstruction suggest that open cool steppe and grass and sedge tundra communities with Poaceae, Cyperaceae, Artemisia, Chenopodiaceae, Caryophyllaceae and Selaginella rupestris dominated the area from 15 to 13.5 kyr BP. On the other hand, the constant presence of Larix pollen in quantities comparable to today's values points to the constant presence of boreal deciduous conifer trees in the regional vegetation during the last glaciation. A major spread of shrub tundra communities, including birch (Betula sect. Nanae), alder (Duschekia fruticosa) and willow (Salix) species, is dated to 13.5-12.7 kyr BP, indicating a noticeable increase in precipitation toward the end of the last glaciation, particularly during the Allerød Interstadial. Between 12.7 and 11.4 kyr BP pollen percentages of herbaceous taxa rapidly increased, whereas shrub taxa percentages decreased, suggesting strengthening of the steppe communities associated with the relatively cold and dry Younger Dryas Stadial. However, the pollen data in hand indicate that Younger Dryas climate was less severe than the climate during the earlier interval from 15 to 13.5 kyr BP. The onset of the Holocene is marked in the pollen record by the highest values of shrub and lowest values of herbaceous taxa, suggesting a return of warmer and wetter conditions after 11.4 kyr BP. Percentages of tree taxa increase gradually and reach maximum values after 7 kyr BP, reflecting the spread of boreal cold deciduous and taiga forests in the region. An interval between 7 and 2 kyr BP is noticeable for the highest percentages of Scots spine (Pinus subgen. Diploxylon), spruce (Picea) and fir (Abies) pollen, indicating mid-Holocene spread of boreal forest communities in response to climate amelioration and degradation of the permafrost layer.

Notas a una estética del olvido

La literatura no se ha mantenido indiferente respecto de sucesos que han dejado marcas en la historia de las sociedades, particularmente aquellos concebidos como traumáticos. Tradicionalmente, las narraciones suscitadas por ellos se sustentan en el trabajo con la memoria y delinean un sujeto que asume el estatuto de testigo narrador. En este marco, ¿resulta factible pensar relatos que se funden en el olvido? Si así lo fuera, ¿qué tipo de sujeto propondrían? Tales cuestiones invitan a pensar y discutir una estética del olvido. Esta estética torna evidentes las limitaciones del lenguaje para abordarlo como objeto y confieren a quien narra una subjetividad diferenciada del sujeto de la memoria, por la cual no intenta superar aquellas dificultades sino que las asume, las expone y las explora. La estética del olvido propone una lectura alternativa a la que lo opone, sin mayores contemplaciones, a la memoria -antinomia en la que el primero de los términos se reviste una valoración negativa-. De mismo modo que autores como Huyssen (2001) y Ric?ur (2004) rescatan las dimensiones políticas y éticas del olvido como elemento constitutivo de la memoria, es posible distinguir en él cierta fertilidad estética que posibilite el surgimiento de un ars oblivionalis

Notas a una estética del olvido

La literatura no se ha mantenido indiferente respecto de sucesos que han dejado marcas en la historia de las sociedades, particularmente aquellos concebidos como traumáticos. Tradicionalmente, las narraciones suscitadas por ellos se sustentan en el trabajo con la memoria y delinean un sujeto que asume el estatuto de testigo narrador. En este marco, ¿resulta factible pensar relatos que se funden en el olvido? Si así lo fuera, ¿qué tipo de sujeto propondrían? Tales cuestiones invitan a pensar y discutir una estética del olvido. Esta estética torna evidentes las limitaciones del lenguaje para abordarlo como objeto y confieren a quien narra una subjetividad diferenciada del sujeto de la memoria, por la cual no intenta superar aquellas dificultades sino que las asume, las expone y las explora. La estética del olvido propone una lectura alternativa a la que lo opone, sin mayores contemplaciones, a la memoria -antinomia en la que el primero de los términos se reviste una valoración negativa-. De mismo modo que autores como Huyssen (2001) y Ric?ur (2004) rescatan las dimensiones políticas y éticas del olvido como elemento constitutivo de la memoria, es posible distinguir en él cierta fertilidad estética que posibilite el surgimiento de un ars oblivionalis

Notas a una estética del olvido

La literatura no se ha mantenido indiferente respecto de sucesos que han dejado marcas en la historia de las sociedades, particularmente aquellos concebidos como traumáticos. Tradicionalmente, las narraciones suscitadas por ellos se sustentan en el trabajo con la memoria y delinean un sujeto que asume el estatuto de testigo narrador. En este marco, ¿resulta factible pensar relatos que se funden en el olvido? Si así lo fuera, ¿qué tipo de sujeto propondrían? Tales cuestiones invitan a pensar y discutir una estética del olvido. Esta estética torna evidentes las limitaciones del lenguaje para abordarlo como objeto y confieren a quien narra una subjetividad diferenciada del sujeto de la memoria, por la cual no intenta superar aquellas dificultades sino que las asume, las expone y las explora. La estética del olvido propone una lectura alternativa a la que lo opone, sin mayores contemplaciones, a la memoria -antinomia en la que el primero de los términos se reviste una valoración negativa-. De mismo modo que autores como Huyssen (2001) y Ric?ur (2004) rescatan las dimensiones políticas y éticas del olvido como elemento constitutivo de la memoria, es posible distinguir en él cierta fertilidad estética que posibilite el surgimiento de un ars oblivionalis

Palynological and geochemical data of sediment core GeoB3910-2 located offshore Northeast Brazil

High resolution palynological and geochemical data of sediment core GeoB 3910-2 (located offshore Northeast Brazil) spanning the period between 19 600 and 14 500 calibrated year bp (19.6-14.5 ka) show a land-cover change in the catchment area of local rivers in two steps related to changes in precipitation associated with Heinrich Event 1 (H1 stadial). At the end of the last glacial maximum, the landscape in semi-arid Northeast Brazil was dominated by a very dry type of caatinga vegetation, mainly composed of grasslands with some herbs and shrubs. After 18 ka, considerably more humid conditions are suggested by changes in the vegetation and by Corg and C/N data indicative of fluvial erosion. The caatinga became wetter and along lakes and rivers, sedges and gallery forest expanded. The most humid period was recorded between 16.5 and 15 ka, when humid gallery (and floodplain) forest and even small patches of mountainous Atlantic rain forest occurred together with dry forest, the latter being considered as a rather lush type of caatinga vegetation. During this humid phase erosion decreased as less lithogenic material and more organic terrestrial material were deposited on the continental slope of northern Brazil. After 15 ka arid conditions returned. During the humid second phase of the H1 stadial, a rich variety of landscapes existed in Northeast Brazil and during the drier periods small pockets of forest could probably survive in favorable spots, which would have increased the resilience of the forest to climate change.

Pollen distribution in marine sediment samples along the south-western African coast

The distribution of pollen in marine sediments is used to reconstruct pathways of terrigenous input to the oceans and provides a record of vegetation change on adjacent continents. The wind transport routes of aeolian pollen is comprehensively illustrated by clusters of trajectories. Isobaric, 4-day backward trajectories are calculated using the modelled wind-field of ECHAM3, and are clustered on a seasonal basis to estimate the main pathways of aeolian particles to sites of marine cores in the south-eastern Atlantic. Trajectories and clusters based on the modelled wind-field of the Last Glacial Maximum hardly differ from those of the present-day. Trajectory clusters show three regional, and two seasonal patterns, determining the pathways of aeolian pollen transport into the south-eastern Atlantic ocean. Mainly, transport out of the continent occurs during austral fall and winter, when easterly and south-easterly winds prevail. South of 25°S, winds blow mostly from the west and southwest, and aeolian terrestrial input is very low. Generally, a good latitudinal correspondence exists between the distribution patterns of pollen in marine surface sediments and the occurrence of the source plants on the adjacent continent. The northern Angola Basin receives pollen and spores from the Congolian and Zambezian forests mainly through river discharge. The Zambezian vegetation zone is the main source area for wind-blown pollen in sediments of the Angola Basin, while the semi-desert and desert areas are the main sources for pollen in sediments of the Walvis Basin and on the Walvis Ridge. A transect of six marine pollen records along the south-western African coast indicates considerable changes in the vegetation of southern Africa between glacial and interglacial periods. Important changes in the vegetation are the decline of forests in equatorial Africa and the north of southern Africa and a northward shift of winter rain vegetation along the western escarpment.

Pollen analysis and age model of sediment core GIK-15856-2

Pollen and spores from a deep-sea core located west of the Niger Delta record an uninterrupted area of lowland rain forest in West Africa from Guinea to Cameroon during the last Interglacial and the early Holocene. During other periods of the last 150 ka, a savanna corridor between the western - Guinean - and the eastern - Congolian - part of the African lowland rain forest existed. This so-called Dahomey Gap had its largest extension during Glacial Stages 6, 4, 3, and 2. Reduced surface salinity in the eastern Gulf of Guinea as recorded by dinoflagellate cysts indicates sufficient precipitation for extensive forest growth during Stages 5 and 1. The large modern extension of dry forest and savanna in West Africa cannot be solely explained by climatic factors. Mangrove expansion in and west of the Niger Delta was largest during the phases of sea-level rise of Stages 5 and 1. During Stages 6, 4, 3, and 2, shelf areas were exposed and the area of the mangrove swamps was minimal.

On the Closure of the Tame Automorphism Group of Affine Three-Space

We provide explicit families of tame automorphisms of the complex affine three-space which degenerate to wild automorphisms. This shows that the tame subgroup of the group of polynomial automorphisms of C3 is not closed, when the latter is seen as an infinite-dimensional algebraic group.

Results of n-alkane biomarker analyses and paleoclimate reconstruction

The current study presents quantitative reconstructions of tree cover, annual precipitation and mean July temperature derived from the pollen record from Lake Billyakh (65°17'N, 126°47'E, 340 m above sea level) spanning the last ca. 50 kyr. The reconstruction of tree cover suggests presence of woody plants through the entire analyzed time interval, although trees played only a minor role in the vegetation around Lake Billyakh prior to 14 kyr BP (<5%). This result corroborates low percentages of tree pollen and low scores of the cold deciduous forest biome in the PG1755 record from Lake Billyakh. The reconstructed values of the mean temperature of the warmest month ~8-10 °C do not support larch forest or woodland around Lake Billyakh during the coldest phase of the last glacial between ~32 and ~15 kyr BP. However, modern cases from northern Siberia, ca. 750 km north of Lake Billyakh, demonstrate that individual larch plants can grow within shrub and grass tundra landscape in very low mean July temperatures of about 8 °C. This makes plausible our hypothesis that the western and southern foreland of the Verkhoyansk Mountains could provide enough moist and warm microhabitats and allow individual larch specimens to survive climatic extremes of the last glacial. Reconstructed mean values of precipitation are about 270 mm/yr during the last glacial interval. This value is almost 100 mm higher than modern averages reported for the extreme-continental north-eastern Siberia east of Lake Billyakh, where larch-dominated cold deciduous forest grows at present. This suggests that last glacial environments around Lake Billyakh were never too dry for larch to grow and that the summer warmth was the main factor, which limited tree growth during the last glacial interval. The n-alkane analysis of the Siberian plants presented in this study demonstrates rather complex alkane distribution patterns, which challenge the interpretation of the fossil records. In particular, extremely low n-alkane concentrations in the leaves of local coniferous trees and shrubs suggest that their contribution to the litter and therefore to the fossil lake sediments might be not high enough for tracing the Quaternary history of the needleleaved taxa using the n-alkane biomarker method.

Case Study of Applied LIP Approach/Activities in the Philippines The Training Services Enhancement Project for Rural Life Improvement (TSEP-RLI) Experience

TSEP-RLI was a technical cooperation project jointly conducted by GOP thru DA-Agricultural Training Institute (ATI) and GOJ thru JICA aimed at institutionalizing the training program for Rural Life Improvement (RLI) at the (ATI). As expected, farmers, fisherfolk, women, youth and extension agents were provided with efficient and effective training services from ATI leading to the improvement of quality of life in the rural areas through efforts of human resource development. The ATI- Bohol was chosen as the model center where participatory trials and various activities of the project were undertaken for five years. These activities were participatory surveys and data collection of on-farm and off-farm productive activities; planning workshop for RLI; feedbacking of survey results and action plans to the community and the Local Government Units (LGUs), and signing of Memorandum of Agreement between the Project and participating LGUs. The above activities were done to facilitate the planning and development of most effective and necessary rural life improvement activities, to confirm the willingness of the people to support and participate and to formalize the partnership between the Project and the LGUs. Since the concept of rural life covers a vast range of activities, a consensus had been reached that the total aspects of rural life be grasped in three spheres, namely, Production & Livelihood (P/L), Rural Living Condition (RLC) and Community Environment (C/E). The RLI for Ubi (Yam) Growers was one of the pilot activities undertaken in two pilot barangays and the target beneficiaries were members of the Rural Improvement Club (RIC- a group of organized women) with the LGU of the Municipality of Corella as the implementing partner. During the planning workshop, the barangay residents articulated their desire to promote production and processing of ubi (sphere on P/L - as the entry point), lack of nutritious food was one of the identified problem (sphere on RLC- expansion point) and environmental degradation such as deforestation, and soil erosion was another problem articulated by the community people (sphere on C/E- expansion point). Major activities that were undertaken namely, Ubi cooking contest, cooking/processing seminar, training courses on entrepreneurial development, ubi production and storage technology, packaging and product design, human resource development and simplified bookkeeping motivated the beneficiaries as well as developed and enhanced their skills & capabilities while strengthening their associations. Their participation to the 5 ubi festivals and other related activities had brought some impacts on their economic and rural life improvement activities. The seven principles of TSEP-RLI include the participatory process, holistic approach, dialogical approach, bottom -up training needs assessment, demand-driven approach, cost sharing approach and collaborative implementation with other agencies including LGUs and the community.