Evaluación ética de la memoria económica de los contratos de ensayos clínicos con medicamentos en España

Objetivos: Analizar el grado de homogeneidad de la memoria económica incluida en los contratos de centros sanitarios españoles participantes en ensayos clínicos (EC) con medicamentos para detectar puntos de potencial conflicto de interés en la investigación clínica. Material y métodos: Se ha analizado, mediante un autocuestionario, la memoria económica de 40 contratos, 31 correspondientes a centros sanitarios privados y públicos seleccionados al azar y 9 correspondientes a las comunidades autónomas con modelo de contrato único. Resultados: El equipo investigador, en el 97,5% de los casos (39 contratos), es el destinatario mayoritario de la remuneración económica por participar en un EC. El porcentaje aportado difiere según el centro, siendo mayor si es público (p=0,021) pero sin especificarse en el 50% de los contratos. En 38 de los 40 contratos analizados no se proporciona un listado de precios de las pruebas complementarias. En el 57,5%, (23 contratos), no se especifica si los gastos de los pacientes son abonados por el promotor. En el 77,5% (31 casos) no se especifica si los gastos derivados de reuniones relacionadas con el EC se incluyen en la memoria económica. Conclusiones: Existe una elevada heterogeneidad en el contenido de la memoria económica. La implantación de un modelo de memoria económica que incluyera una cantidad económica de remuneración fija por cada paciente reclutado por parte del promotor, para todos los centros participantes, podría disminuir las desigualdades entre centros, los conflictos de intereses, y además, incrementaría la trasparencia y la calidad de los EC.Abstract: Objectives: To analyze the homogeneity of the economic report of the contracts of Spanish medical centers participating in clinical trials with medicinal products for detecting points of potential conflict of interest in clinical research. Material and methods: We analyzed, through a selfautoquestionnaire, the budgetary information of the 40 contracts, 31 of them corresponding to public and private healthcare centers, randomly selected, and 9 corresponding to the Spanish regions who have only a model contract. Results: The investigator team is the recipient majority (97.5% of cases) the economic remuneration for participating in a clinical trial. The percentage differs according to the center considered, being greater in the public setting (p=0.021) but no specified in 50% of the contracts. In 38 of the 40 contracts analyzed a price list of tests is not provided. In 57.5% of the patients are paid by the promoter. In 17.5% failed to mention that the comparative drug to be supplied free of charge. And, 77.5% did not specify whether the costs of meetings relating to the clinical trial or not to include in the expenses of the promoter. Conclusions: There is a high heterogeneity in the content of the budgetary information. The implementation of a single contract model would reduce the inequalities between schools, conflict of interest and increase transparency and quality of the clinical trial

Soil penetration resistance and tree root development

Current UK guidance suggests that a 'rootable' soil profile of at least 1.0 m depth should be sufficient to allow adequate rooting of the majority of tree species in a range of soil types and climatic conditions [Arboricultural Journal (1995) vol. 19, 19-27]. However, there is some uncertainty as to what constitutes a loosened soil profile in terms of penetration resistance. In this study the root development of Italian alder, Japanese larch, Corsican pine and birch was assessed after 5 years of tree growth. These data were compared to penetration resistance measured using both a cone penetrometer and a 'lifting driving tool' (dropping weight penetrometer). Tree root number and percentage were significantly reduced by increasing soil penetration resistance measured with both the cone penetrometer (P < 0.050) and the 'lifting driving tool' (P = 0.011 and 0.008 respectively). The vast majority of roots were recorded in soils with a penetration resistance of less than 3 MPa (90.7%) with a significant amount in the less than 2 MPa class (70.2%). Root development of Italian alder, Japanese larch and birch all showed a similar pattern, but Corsican pine appeared to be capable of rooting into more compact soils. The 'lifting driving tool' can be used as an alternative measure of soil penetration resistance. This equipment is more cost effective, easier to use and capable of measurements at a greater depth than the cone penetrometer. The majority of Japanese larch and birch roots (84.3%) were recorded in soils where it took less than 15 impacts to penetrate one 10 cm soil depth increment. The modelled data also suggest that a penetration resistance of 2 and 2.5 MPa relates to 10 and 15 impacts respectively. © 2008 Forestry Commission, Crown copyright

How do Zimbabweans value health states?

Background Quality of life weights based on valuations of health states are often used in cost utility analysis and population health measures. This paper reports on an attempt to develop quality of life weights within the Zimbabwe context. Methods 2,384 residents in randomly selected small residential plots of land in a high-density suburb of Harare valued descriptors of 38 health states based on different combinations of the five domains of the EQ-5D (mobility, self-care, usual activities, pain or discomfort and anxiety or depression). The English version of the EQ-5D was used. The time trade-off method was used to determine the values, and 19,020 individual preferences for health states were analysed. A residual maximum likelihood linear mixed model was used to estimate a function for predicting the values of all possible combinations of levels on the five domains. The model was fit to a random subset of two-thirds of the observations, with the remaining observations reserved for analysis of predictive validity. The results were compared to a similar study undertaken in the United Kingdom. Results A credible model was developed to predict the values of states that were not valued directly. In the subset of observations reserved for validation, the mean absolute difference between predicted and observed values was 0.045. All domains of the EQ-5D were found to contribute significantly to the model, both at the moderate and severe levels. Severe pain was found to have the largest negative coefficient, followed by the inability to wash and dress oneself. Conclusion Despite a generally lower education level than their European counterparts, urban Zimbabweans appear to value health states in a consistent manner, and the determination of a global method of establishing quality of life weights may be feasible and valid. However, as the relative weightings of the different domains, although correlated, differed from the standard set of weights recommended by the EuroQol Group, the locally determined coefficients should be used within the Zimbabwean context

Effect of restricting silage feeding prepartum on time of calving, dystocia and stillbirth in Holstein-Friesian cows

A study was carried out to investigate the effect of restricting silage feeding on time of calving and calving performance in Holstein-Friesian cows. In the treatment group (n = 1,248 cows, 12 herds) silage feeding commenced in the evening (17:00 to 20:00 h), after a period of restricted access (2 to 10 h) while in the control group ad-libitum access to silage was provided over the 24 h period (n = 1,193 cows, 12 herds). Daytime and nighttime calvings were defined as calvings occurring between the hours of 06:30 and 00:29 and between 00:30 and 06:29, respectively. Restricting access to silage resulted in less calvings at night compared to cows with ad-libitum access to silage (18 vs 22%, P < 0.05). Cows with restricted access to silage had a higher percentage of difficult calvings (11 vs 7%, P < 0.001) and stillbirths (7 vs 5%, P < 0.05) compared to cows in the control group. The percentage of calvings at night was lower (13%) when access to silage was restricted for 10 h compared to 2, 4 or 6 h (22, 18, 25%, respectively) (P < 0.001). Calf sire breed, calf gender or cow parity did not influence time of calving. In conclusion, offering silage to pregnant Holstein-Friesian cows in the evening, after a period of restricted access, reduced the incidence of nighttime calvings, but increased the incidence of dystocia and stillbirth

The efficacy of three techniques to alleviate soil compaction at a restored sand and gravel quarry

Reinstated soil at restored sites often suffers from severe compaction which can significantly impede root development. Several methods, such as ripping and complete cultivation, are available to alleviate compaction that may occur as a result of soil reinstatement. This paper examines the effectiveness of the industry standard industrial ripper and a prototype modern ripper, the Mega-Lift, in comparison with the recommended best practice method of complete cultivation. An investigation of the penetration resistance of the soil at a restored sand and gravel quarry was carried out using a cone penetrometer and a 'lifting driving tool' (dropping weight penetrometer) 3 years following cultivation. All the cultivation treatments reduced soil compaction to some degree compared with the untreated control. However, the penetration resistance values suggest that rooting would be restricted at relatively shallow depths in the plots cultivated using the industrial and Mega-Lift ripper; penetration resistance exceeded 2 MPa within the first 0.33 m. Complete cultivation maintained penetration resistance values of less than 2 MPa within the depth limit of the penetrometer of 0.42 m. In addition, the results from the 'lifting driving tool' indicate that soils treated using complete cultivation remained significantly looser than those treated with the ripper to a depth of at least 0.80 m. The results demonstrate that complete cultivation remains the most effective method of alleviating soil compaction on restored sites, although it is recognized that its relatively high cost may restrict the uptake of the technique. © 2006 Forest Research. Crown copyright

Analysis of leaf appearance, leaf death and phoma leaf spot, caused by Leptosphaeria maculans, on oilseed rape (Brassica napus) cultivars

The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright Association of Applied BiologistsDevelopment of phoma leaf spot (caused by Leptosphaeria maculans) on winter oilseed rape (canola, Brassica napus) was assessed in two experiments at Rothamsted in successive years (2003-04 and 2004-05 growing seasons). Both experiments compared oilseed rape cultivars Eurol, Darmor, Canberra and Lipton, which differ in their resistance to L. maculans. Data were analysed to describe disease development in terms of increasing numbers of leaves affected over thermal time from sowing. The cultivars showed similar patterns of leaf spot development in the 2003-04 experiment when inoculum concentration was relatively low (up to 133 ascospores m-3 air), Darmor developing 5.3 diseased leaves per plant by 5 May 2004, Canberra 6.6, Eurol 6.8 and Lipton 7.5. Inoculum concentration was up to sevenfold greater in 2004-05, with Eurol and Darmor developing 2.4 diseased leaves per plant by 16 February 2005, whereas Lipton and Canberra developed 2.8 and 3.0 diseased leaves, respectively. Based on three defined periods of crop development, a piece-wise linear statistical model was applied to the progress of the leaf spot disease (cumulative diseased leaves) in relation to appearance ('birth') and death of leaves for individual plants of each cultivar. Estimates of the thermal time from sowing until appearance of the first leaf or death of the first leaf, the rate of increase in number of diseased leaves and the area under the disease progress line (AUDPL) for the first time period were made. In 2004-05, Canberra (1025 leaves x degrees C days) and Lipton (879) had greater AUDPL values than Eurol (427) and Darmor (598). For Darmor and Lipton, the severity of leaf spotting could be related to the severity of stem canker at harvest. Eurol had less leaf spotting but severe stem canker, whereas Canberra had more leaf spotting but less severe canker.Peer reviewe

Toxic effects of Pb2+ on growth of cowpea (Vigna unguiculata)

A concentration as low as 1 mu M lead (Pb) is highly toxic to plants, but previous studies have typically related plant growth to the total amount of Pb added to a solution. In the present experiment, the relative fresh mass of cowpea (Vigna unguiculata) was reduced by 10% at a Pb2+ activity of 0.2 mu M for the shoots and at a Pb2+ activity of 0.06 mu M for the roots. The primary site of Pb2+ toxicity was the root, causing severe reductions in root growth, loss of apical dominance (shown by an increase in branching per unit root length), the formation of localized swellings behind the root tips (due to the initiation of lateral roots), and the bending of some root tips. In the root, Pb was found to accumulate primarily within the cell walls and intercellular spaces. (C) 2007 Elsevier Ltd. All rights reserved

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension ban castrated with or without analgesia: 2. responses related to stress, health and productivity

Tension banding castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the banders as a humane castration method. Two experiments were conducted, under tropical conditions using Bos indicus bulls comparing tension banding (Band) and surgical (Surgical) castration of weaner (7-10 months old) and mature (22-25 months old) bulls with and without pain management (NSAID (ketoprofen) or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a range of measures; this paper reports on some physiological, morbidity and productivity-related responses to augment the behavioural responses reported in an accompanying paper. Blood samples were taken on the day of castration (day 0) at the time of restraint (0. min) and 30. min (weaners) or 40. min (mature bulls), 2. h, and 7. h; and days 1, 2, 3, 7, 14, 21 and 28 post-castration. Plasmas from day 0 were assayed for cortisol, creatine kinase, total protein and packed cell volume. Plasmas from the other samples were assayed for cortisol and haptoglobin (plus the 0. min sample). Liveweights were recorded approximately weekly to 6 weeks and at 2 and 3 months post-castration. Castration sites were checked at these same times to 2 months post-castration to score the extent of healing and presence of sepsis. Cortisol concentrations (mean. ±. s.e. nmol/L) were significantly (

Parthenogenesis did not consistently evolve in insular populations of Ischnura hastata (Odonata, Coenagrionidae)

1. The evolutionary advantages that have driven the evolution of sex are still very much debated, and a number of benefits of parthenogenesis over sexual reproduction have been proposed. In particular, parthenogenetic individuals are thought to exhibit higher probabilities of establishment following arrival in new, isolated habitats such as islands. 2. One notable example of parthenogenesis occurring in islands is the damselfly Ischnura hastata, an American species that has colonised the Azores archipelago, where the populations consist only of females. This is the only known example of parthenogenesis within the insect order Odonata. 3. Here, two island populations of I. hastata were studied, one in the Galapagos and one in Cuba, to test whether island colonisation is consistently associated with parthenogenesis in this species. Field capture-mark-recapture studies and laboratory rearing of field-collected eggs were undertaken in both areas. 4. Sex ratios in the field were found to be heavily female-biased among mature individuals; however, fertility rates of field-collected eggs were high, and the sex ratios in the laboratory did not differ from 1:1. Data from laboratory rearing showed that shorter larval development times and shorter adult life spans in males result in protandry, which might explain the skewed sex ratios in the field. 5. These findings are consistent with sex differences in key demographic parameters which could predispose I. hastata to parthenogenesis. However, the Azores population of I. hastata remains the only documented case of asexual reproduction in this insect group

GCN2-dependent phosphorylation of eukaryotic translation initiation factor-2α in Arabidopsis

The yeast regulatory protein kinase, general control non-derepressible-2 (GCN2) plays a key role in general amino acid control. GCN2 phosphorylates the α subunit of the trimeric eukaryotic translation initiation factor-2 (eIF2), bringing about a decrease in the general rate of protein synthesis but an increase in the synthesis of GCN4, a transcription factor that promotes the expression of genes encoding enzymes for amino acid biosynthesis. The present study concerned the phosphorylation of Arabidopsis eIF2α (AteIF2α) by the Arabidopsis homologue of GCN2, AtGCN2, and the role of AtGCN2 in regulating genes encoding enzymes of amino acid biosynthesis and responding to virus infection. A null mutant for AtGCN2 called GT8359 was obtained and western analysis confirmed that it lacked AtGCN2 protein. GT8359 was more sensitive than wild-type Arabidopsis to herbicides that affect amino acid biosynthesis. Phosphorylation of AteIF2α occurred in response to herbicide treatment but only in wild-type Arabidopsis, not GT8359, showing it to be AtGCN2-dependent. Expression analysis of genes encoding key enzymes for amino acid biosynthesis and nitrate assimilation revealed little effect of loss of AtGCN2 function in GT8359 except that expression of a nitrate reductase gene, NIA1, was decreased. Analysis of wild-type and GT8359 plants infected with Turnip yellow mosaic virus or Turnip crinkle virus showed that AteIF2α was not phosphorylated