Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group

Background: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. Objective: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. Methods: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). Results: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. Conclusion: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

Speciation and phylogeography in Caridina indistincta, a complex of freshwater shrimps from Australian heathland streams

The Caridina indistincta complex is a group of closely related atyid shrimps that inhabit coastal freshwater streams throughout north-eastern Australia. Using mitochondrial DNA sequence data (cytochrome oxidase 1, CO1), we (1) inferred the timing of speciation in the C. indistincta group and (2) examined the intraspecific phylogeographic patterns within the group. Assuming a shrimp-specific rate of CO1 evolution, the level of sequence divergence among species suggests that speciation took place during the Miocene epoch. Within one widespread mainland species, phylogeographic patterns suggest strong geographic 'regionalisation' of mtDNA lineages that are most likely of Pleistocene origin. By contrast, another species comprises two highly divergent mtDNA lineages that occur in sympatry. We suggest that although Pleistocene sea-level regressions appear important in generating population-level phylogeographic patterns, these events were largely unimportant in the formation of species in this group.

Expression of ephs and ephrins in developing mouse inner ear

Levels of expression of mRNAs encoding the different Ephs and ephrins were measured by semi-quantitative reverse-transcription polymerase chain reaction in developing mouse whole inner ears, and in dissected fractions of the neonatal mouse inner ear. Nineteen of the 24 known Ephs and ephrins were surveyed. The results showed that between embryonic age (E) 11.5 days and E12.5, levels increased 10-300 times per unit of tissue. In neonatal mice, the fraction containing combined organ of Corti and spiral ganglion showed relatively strong expression of EphA4, EphB3, ephrin-A3, ephrin-B2 and ephrin-B3. In the lateral wall, EphA4, ephrin-A3 and ephrin-B2 were strongly expressed, while ephrin-A3 was particularly strongly expressed in utricular and saccular sensory epithelia. The results suggest that the Ephs and ephrins are likely to play a part in the differentiation of the structures of the inner ear, and show which Ephs and ephrins are most likely to play important roles in the different structures. (C) 2003 Elsevier Science B.V. All rights reserved.

Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity

This paper investigates the possible link between non-workplace cadmium (Cd) exposure, cytochrome P450 expression and hypertension. We present results of our investigation into the relationships between liver and kidney Cd burdens and the abundance of the CYP isoform 4A11. Our data show associations between non-workplace Cd exposure and changes in the abundance of hepatic and renal cortical CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were positively correlated with tissue Cd content while in contrast CYP4A11 abundance was inversely correlated with kidney Cd burden. These differences are most likely related to the different Cd burden of the tissues. These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform. Potential mechanisms by which Cd may alter CYP4A11 expression are discussed briefly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Field hydraulic properties of an Alfisol under various fallow systems in southwestern Nigeria

The effects of various fallow management systems and cropping intensities on water infiltration were measured on an Alfisol at Ibadan in southwestern Nigeria. The objective was to determine the influence of the land use systems (a combination of crop-fallow sequences and intercropping types) on soil hydraulic properties obtained by disc permeameter and double-ring infiltration measurements. The experiment was established in 1989 as a split-plot design with four replications. The main plots were natural fallow, planted Pueraria phaseoloides and planted Leucaena leucocephala. The subplots were 1 year of maize/cassava intercrop followed by 3-year fallow (25% cropping intensity), or 2-year fallow (33% cropping intensity), or 1-year fallow (50% cropping intensity), or no fallow period (100% cropping intensity). Water infiltration rates and sorptivities were measured under saturated and unsaturated flow. Irrespective of land use, infiltration rates at the soil surface (121-324 cm h(-1)) were greater than those measured at 30 cm depth (55-144 cm h(-1)). This indicated that fewer large pores were present below 30 cm depth compared with 0-30 cm, depth. Despite some temporal variation, sorptivities with the highest mean value of 93.5 cm h(-1/2) increased as the cropping intensity decreased, suggesting a more continuous macropore system under less intensive land use systems. This was most likely due to continuous biopores created by perennial vegetation under long fallow systems. Intercropped maize and cassava yields also increased as cropping intensity decreased. The weak relationship between crop yields and hydraulic conductivity/infiltration rates suggests that the rates were not limiting.

Effect of time of harvest of budded virus on the selection of baculovirus FP mutants in cell culture

Rapid formation and selection of FP (few polyhedra) mutants occurs during serial passaging of Helicoverpa armigera nucleopolyhedrovirus (HaSNPV) in insect cell culture. The production of HaSNPV for use as biopesticides requires the passaging of the virus over a number of passages to produce enough virus inoculum for large-scale fermentation. During serial passaging in cell culture, FP mutants were rapidly selected, resulting in declined productivity and reduced potency of virus. Budded virus (BV) is usually harvested between 72 and 96 h postinfection (hpi) in order to obtain a high titer virus stock. In this study, the effect of tine of harvest (TOH) for BV on the selection rate of HaSNPV FP mutants during serial passaging was investigated. BV were harvested at different times postinfection, and each series was serially passaged for six passages. The productivity and percentage of FP mutants at each passage were determined. It was found that the selection of FP mutants can he reduced by employing an earlier TOH for BV. Serial passaging with BV harvested at 48 hpi showed a slower accumulation of FP mutants compared to that of BV harvested after 48 hpi. Higher cell specific yields were also maintained when BV were harvested at 48 hpi. When BV that were formed between 48 and 96 hpi were harvested and serially passaged, FP mutants quickly dominated the virus population. This suggests that the V formed and released between 48 and 96 hpi are most likely from FP mutant infected cells.

The Utility of the Human Security Agenda for Policy-makers

The idea of “human security” is gaining attention among policy-makers and security analysts. Little scholarly attention has been given to the questions of why states accept (or reject) a human security agenda or how such an agenda is incorporated into policy practices. The article suggests that a human security approach is most likely to be applied when both humanitarian and national interests combine. Yet when states or organisations adopt a human security approach, they often misjudge the complex and long-term commitment required of such an approach. There is also the potential for such an agenda to be manipulated to justify questionable courses of action. These issues frame an analysis of six recent case studies.

Introdu????o ?? cr??tica da raz??o desestatizante

O artigo compreende uma vis??o cr??tica sobre os processos de reestrutura????o do Estado baseados na l??gica neoliberal, que caracterizam as reformas minimalistas da d??cada de 80. O tema da reforma do Estado ?? visto como um dos grandes desafios intelectuais e pol??ticos deste fim de s??culo, devendo necessariamente ser contextualizado historicamente, uma vez que n??o existe uma ??nica crise do Estado, mas v??rias crises dos Estados espec??ficas e particulares, cujas solu????es n??o s??o ??nicas nem universais, mas dependentes do diagn??stico de cada caso. Entende-se que a raz??o desestatizante apresenta limita????es, reconhecidas at?? mesmo pelas institui????es financeiras internacionais que antes a defendiam. O cen??rio de um novo modo de atua????o estatal ?? apresentado como mais prov??vel, sendo o conceito de reestatiza????o mais adequado para as mudan??as que se fazem necess??rias.

Análise de fatores geográficos e climáticos relacionados à distribuição de Phlebotominae (Diptera: Psychodidae) em área de transmissão de leishmaniose tegumentar americana no estado do Espírito Santo, Brasil

A leishmaniose tegumentar americana (LTA) é uma doença que acomete pele e mucosas causada por parasitos dermotrópicos do gênero Leishmania Ross, 1903. Os parasitos são transmitidos através da picada de pequenos dípteros da família Psychodidae, os flebotomíneos. O município de Cariacica, Espírito Santo, Brasil, esteve nos últimos cinco anos (2009 a 2013) entre os cinco que apresentaram maior número de casos notificados no estado, segundo a Secretaria de Estado de Saúde (SESA-ES, 2014). A localidade de Roda D’Água demonstra grande importância, por concentrar elevado número de casos, contribuindo com grande parte das notificações do município. Avaliando os casos da doença na região, registrados nos prontuários médicos do serviço de referência, na Unidade de Medicina Tropical da Universidade Federal do Espírito Santo, observou-se que estes ocorriam a até 550 m de altitude, numa área que vai de 20 a 718 m. A hipótese mais provável seria a de que o fenômeno fosse relacionado aos vetores, já que o homem e os animais estariam presentes em todas as altitudes. De fevereiro de 2002 a janeiro de 2004 foram realizadas coletas mensais de flebotomíneos em Roda D’Água, que aconteciam simultaneamente em três níveis de altitude, sendo: nível 1 - até 250 m; nível 2 - entre 250 e 500m e nível 3 - acima de 500m. Em cada nível as coletas aconteciam em dois ambientes: mata e peridomicílio. As capturas eram feitas em armadilhas de Shannon modificadas e por busca ativa em repouso, com capturador de Castro. Avaliou-se o comportamento das espécies quanto à pluviosidade (períodos seco e chuvoso) e às estações do ano. Analisaram-se estatisticamente as principais espécies antropofílicas de importância epidemiológica (Falqueto, 1995). Foram calculados os índices ecológicos abundância, riqueza, diversidade, equitabilidade e dominância. Coletou-se um total de 13233 flebotomíneos, com identificação de 23 espécies. A espécie predominante foi Nyssomyia intermedia (61,12%), seguida por Pintomyia fischeri (18,20%) e Migonemyia migonei (8,68%), todas antropofílicas. Somou-se a estas a espécie Pintomyia monticola, que representou 1,67% do total de espécimes coletados e também é altamente antropofílica. As demais espécies somaram 10,10% do total de flebotomineos. A altitude influenciou a distribuição das quatro espécies analisadas, tendo Ny. intermedia e Pi. fischeri sido mais abundantes no nível 2, Mg. migonei mais abundante no nível 1 e Pi. monticola no nível 3. Em relação ao ambiente, as espécies Ny. intermedia e Mg. migonei foram estatisticamente mais abundantes no peridomicílio e Pi. monticola na mata. A distribuição de Pi. fisheri não apresentou diferença significativa entre os dois ambientes, porém foi a única afetada pelas chuvas e estações do ano, sendo a espécie mais encontrada no período seco e no inverno. Nyssomyia intermedia parece ser a principal espécie vetora da LTA em Roda D’Água, com Mg. migonei provavelmente tendo papel secundário. Pi. fisheri não parece estar envolvido localmente na transmissão da doença para humanos, apesar de já ter sido incriminado em outras regiões. A distribuição de Pi. monticola em relação à altitude e ao ambiente indica ser improvável sua participação na transmissão da LTA naquela região.

25 de Abril para sempre? "Fascismo" nunca mais?

Nem está garantido que o “25 de Abril seja para sempre”. O mais certo é que não esteja. Nem está assegurado, qual verdade ontológica, que não haverá mais “fascismo” ou um outro “Estado Novo de inspiração fascista”, como alguns preferem descrever o período histórico vivido em Portugal entre 1933 (com raízes em 1928 após eleição de Óscar Carmona) e o 25 de Abril de 1974. O mais certo é que surjam novos tipos de “fascismo”. § Abstract: Neither is guaranteed that the "April 25th is forever." Most likely it is not. Neither is assured, what ontological truth, there will be no more "fascism" or another "New State of fascist inspiration," as some prefer to describe the historical period lived in Portugal between 1933 (with roots in 1928 after Óscar Carmona Election) and April 25, 1974. most likely there are new types of "fascism."

Predictors of Successful Weight Control: Cross-Cultural Moderators of Treatment Outcomes

Given the heterogeneity of effect sizes within the population for any treatment, identifying moderators of outcomes is critical [1]. In weight management programs, there is a high individual variability in terms of weight loss and an overall modest success [2]. Some people will adopt and sustain attitudes and behaviors associated with weight loss, while others won’t [3]. To predict weight loss outcome just from the subject’s baseline information would be very valuable [4,5]. It would allow to: - Better match between treatments and individuals - Identify the participants with less probability of success (or potential dropouts) in a given treatment and direct them to alternative therapies - Target limited resources to those most likely to succeed - Increase cost-effectiveness and improve success rates of the programs Few studies have been dedicated to describe baseline predictors of treatment success. The Healthy Weight for Life (USA) study is one of the few. Its findings are now being cross-validated in Portuguese samples. This paper describes these cross-cultural comparisons.

Analysis of constructed wetland performance for irrigation reuse

Most of the wastewater treatment systems in small rural communities of the Cova da Beira region (Portugal) consist of constructed wetlands (CW) with horizontal subsurface flow (HSSF). It is believed that those systems allow the compliance of discharge standards as well as the production of final effluents with suitability for reuse. Results obtained in a nine-month campaign in an HSSF bed pointed out that COD and TSS removal were lower than expected. A discrete sampling also showed that removal of TC, FC and HE was not enough to fulfill international irrigation goals. However, the bed had a very good response to variation of incoming nitrogen loads presenting high removal of nitrogen forms. A good correlation between mass load and mass removal rate was observed for BOD5, COD, TN, NH4-N, TP and TSS, which shows a satisfactory response of the bed to the variable incoming loads. The entrance of excessive loads of organic matter and solids contributed for the decrease of the effective volume for pollutant uptake and therefore, may have negatively influenced the treatment capability. Primary treatment should be improved in order to decrease the variation of incoming organic and solid loads and to improve the removal of COD, solids and pathogenic. The final effluent presented good physical-chemical quality to be reused for irrigation, which is the most likely application in the area.

Multi-stage evolution of a sub-aerial volcanic ridge over the last 1.3 Myr: S. Jorge Island, Azores Triple Junction

New K/Ar dating and geochemical analyses have been carried out on the WNW-ESE elongated oceanic island of S. Jorge to reconstruct the volcanic evolution of a linear ridge developed close to the Azores triple junction. We show that S. Jorge sub-aerial construction encompasses the last 1.3 Myr, a time interval far much longer than previously reported. The early development of the ridge involved a sub-aerial building phase exposed in the southeast end of the island and now constrained between 1.32 +/- 0.02 and 1.21 +/- 0.02 Ma. Basic lavas from this older stage are alkaline and enriched in incompatible elements, reflecting partial melting of an enriched mantle source. At least three differentiation cycles from alkaline basalts to mugearites are documented within this stage. The successive episodes of magma rising, storage and evolution suggest an intermittent reopening of the magma feeding system, possibly due to recurrent tensional or trans-tensional tectonic events. Present data show a gap in sub-aerial volcanism before a second main ongoing building phase starting at about 750 ka. Sub-aerial construction of the S. Jorge ridge migrated progressively towards the west, but involved several overlapping volcanic episodes constrained along the main WNW-ESE structural axis of the island. Malic magmas erupted during the second phase have been also generated by partial melting of an enriched mantle source. Trace element data suggest, however, variable and lower degrees of partial melting of a shallower mantle domain, which is interpreted as an increasing control of lithospheric deformation on the genesis and extraction of primitive melts during the last 750 kyr. The multi-stage development of the S. Jorge volcanic ridge over the last 1.3 Myr has most likely been greatly influenced by regional tectonics, controlled by deformation along the diffuse boundary between the Nubian and the Eurasian plates, and the increasing effect of sea-floor spreading at the Mid-Atlantic Ridge.

Age transition of tuberculosis incidence and mortality in Brazil

OBJECTIVE: Before the Aids pandemic, demographic transition and control programs prompted a shift in the age of incidence of tuberculosis from adults to older people in many countries. The objective of the study is to evaluate this transition in Brazil. METHODS: Tuberculosis incidence and mortality data from the Ministry of Health and population data from the Brazilian Bureau of Statistics were used to calculate age-specific incidence and mortality rates and medians. RESULTS: Among reported cases, the proportion of older people increased from 10.5% to 12% and the median age from 38 to 41 years between the period of 1986 and 1996. The smallest decrease in the incidence rate occurred in the 30--49 and 60+ age groups. The median age of death increased from 53 to 55 years between 1980 and 1996. The general decline in mortality rates from 1986 to 1991 became less evident in the 30+ age group during the period of 1991 to 1996. A direct correlation between age and mortality rates was observed. The largest proportion of bacteriologically unconfirmed cases occurred in older individuals. CONCLUSIONS: The incidence of tuberculosis has begun to shift to the older population. This shift results from the decline in the annual risk of infection as well as the demographic transition. An increase in reactivation tuberculosis in older people is expected, since this population will grow from 5% to 14% of the Brazilian population over the next 50 years. A progressive reduction in HIV-related cases in adults will most likely occur. The difficulty in diagnosing tuberculosis in old age leads to increased mortality.

Boulder deposition during major tsunami events

A remarkable accumulation of marine boulders located above the present spring tide level has occurred in two coastal lowlands of the Algarve (Portugal). The size-interval of the particles studied here is seldom reported in the literature in association with extreme events of coastal inundation, thus making this study of relevance to many other coasts worldwide. The spreads of boulders extend several hundred meters inland and well beyond the present landward limit of storm activity. The marine origin of the boulders is demonstrated by well-developed macro-bioerosion sculpturing and in situ skeletal remains of endolithic shallow marine bivalves. The good state preservation of the fossils within the boulders indicates that abrasion duringtransport and redeposition was not significant. We envisage boulder deposition as having taken place during the Lisbon tsunami of ad 1755 through the simultaneous landward entrainment of coarse particles from nearshore followed by rapid shoreward suspended-dominated transport and non-graded redeposition that excluded significant sorting by weight or boulder dimensions. We use numerical hydrodynamic modeling of tsunami (and storm) waves to test the observational data on boulder dimensions (density, size, distribution) on the most likely processes of sediment deposition. This work demonstrates the effectiveness of the study of boulder deposits in tsunami reconstruction. Copyright (C) 2011 John Wiley & Sons, Ltd.