975 research outputs found

    Salinity guidelines for irrigation: Case studies from Water Research Commission projects along the Lower Vaal, Riet, Berg and Breede Rivers

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    A vast number of projects on salinity in irrigated agriculture were funded by the Water Research Commission (WRC) during the past 40 years. However, due to the diversity of the projects it is virtually impossible to cover all  aspects thoroughly in a paper of limited length. Thus this review focuses mainly on projects along the Lower Vaal, Riet, Berg and Breede Rivers in South Africa. The results on the water quality of these rivers indicate that irrigation has led to the deterioration of water sources. There is a direct relationship between river water quality and soils irrigated. Fortunately, effective land-suitability guidelines were developed and applied during the establishment of the major irrigation schemes. This facilitated the management of soils under irrigation. The results from long-term irrigation case studies along the Lower Vaal River and Breede River show that the quality of soils can be improved. The opposite is also true where mismanagement occurred. Research on the salinity threshold of major crops (grapevines, wheat, maize, groundnuts, etc.) confirmed the empiric nature of the guidelines. It is suggested that a more dynamic approach be used for managing salinity under irrigation at farm level, i.e. the use of models. Amongst others, future research should focus on determining the spatial and temporal distribution of salt in irrigated soils.Keywords: crop response, electrical conductivity, sodium adsorption ratio, soil type, water qualit

    Primary ovarian cancer chemotherapy: current standards of care

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    Chemotherapy has been regarded as standard therapy for the majority of women with advanced epithelial ovarian cancer for several decades, with this role filled largely by the alkylating agents — used as monotherapy — until the mid-1980s. The activity of cisplatin in this disorder was established during the 1970s, and combinations of cisplatin and an alkylating agent were widely used during the late 1980s. However, further research prompted by continuing concerns over poor survival and tolerability led to the adoption of paclitaxel in combination with either cisplatin or carboplatin as first-line therapy in ovarian cancer during the 1990s. Most recent research has focused on further optimisation of these regimens to maximise clinical benefit while minimising toxicity, and investigations into alternative taxanes (e.g. docetaxel), other novel agents and new treatment schedules are ongoing

    Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

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    BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

    Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

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    There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

    Patterns of Interspecific Variation in the Heart Rates of Embryonic Reptiles

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    New non-invasive technologies allow direct measurement of heart rates (and thus, developmental rates) of embryos. We applied these methods to a diverse array of oviparous reptiles (24 species of lizards, 18 snakes, 11 turtles, 1 crocodilian), to identify general influences on cardiac rates during embryogenesis. Heart rates increased with ambient temperature in all lineages, but (at the same temperature) were faster in lizards and turtles than in snakes and crocodilians. We analysed these data within a phylogenetic framework. Embryonic heart rates were faster in species with smaller adult sizes, smaller egg sizes, and shorter incubation periods. Phylogenetic changes in heart rates were negatively correlated with concurrent changes in adult body mass and residual incubation period among the lizards, snakes (especially within pythons) and crocodilians. The total number of embryonic heart beats between oviposition and hatching was lower in squamates than in turtles or the crocodilian. Within squamates, embryonic iguanians and gekkonids required more heartbeats to complete development than did embryos of the other squamate families that we tested. These differences plausibly reflect phylogenetic divergence in the proportion of embryogenesis completed before versus after laying

    First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

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    Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer

    A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

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    Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

    Small Tympanic Membrane Perforations in the Inferior Quadrants Do Not Impact the Manubrium Vibration in Guinea Pigs

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    BACKGROUND: It has been believed that location of the perforation has a significant impact on hearing loss. However, recent studies have demonstrated that the perforation sites had no impact on hearing loss. We measured the velocity and pattern of the manubrium vibration in guinea pigs with intact and perforated eardrum using a laser Doppler vibrometer in order to determine the effects of different location perforations on the middle ear transfer functions. METHODS: Two bullas from 2 guinea pigs were used to determine stability of the umbo velocities, and 12 bullas from six guinea pigs to determine the effects of different location perforations on sound transmission. The manubrium velocity was measured at three points on the manubrium in the frequencies of 0.5-8 kHz before and after a perforation was made. The sites of perforations were in anterior-inferior (AI) quadrants of left ears and posterior-inferior (PI) quadrants of right ears. RESULTS: The manubrium vibration velocity losses were noticed in the perforated ears only below 1.5 kHz. The maximum velocity loss was about 7 dB at 500 Hz with the PI perforation. No significant difference in the velocity loss was found between AI and PI perforations. The average ratio of short process velocity to the umbo velocity was approximately 0.5 at all frequencies. No significant differences were found before and after perforation at all frequencies (p>0.05) except 7 kHz (p = 0.004) for both AI and PI perforations. CONCLUSIONS: The manubrium vibration velocity losses from eardrum perforation were frequency-dependent and the largest losses occur at low frequencies. Manubrium velocity losses caused by small acute inferior perforations in guinea pigs have no significant impact on middle ear sound transmission at any frequency tested. The manubrium vibration axis may be perpendicular to the manubrium below 8 kHz in guinea pigs
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