Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.

Application of spatial analysis techniques to adjust for fertility trends and identify interplot competition in early stage sugarcane selection trials

Most sugarcane breeding programs in Australia use large unreplicated trials to evaluate clones in the early stages of selection. Commercial varieties that are replicated provide a method of local control of soil fertility. Although such methods may be useful in detecting broad trends in the field, variation often occurs on a much smaller scale. Methods such as spatial analysis adjust a plot for variability by using information from immediate neighbours. These techniques are routinely used to analyse cereal data in Australia and have resulted in increased accuracy and precision in the estimates of variety effects. In this paper, spatial analyses in which the variability is decomposed into local, natural, and extraneous components are applied to early selection trials in sugarcane. Interplot competition in cane yield and trend in sugar content were substantial in many of the trials and there were often large differences in the selections between the spatial and current method used by the Bureau of Sugar Experiment Stations. A joint modelling approach for tonnes sugar per hectare in response to fertility trends and interplot competition is recommended.

Yield response of rice (Oryza sativa L.) genotypes to different types of drought under rainfed lowlands - Part 2. Selection of drought resistant genotypes

Drought frequently reduces grain yield of rainfed lowland rice. A series of experiments were conducted in drought-prone northeast Thailand to study the magnitude and consistency of yield responses of diverse, rainfed lowland rice genotypes to drought stress environments and to examine ways to identify genotypes that confer drought resistance. One hundred and twenty-eight genotypes were grown under non-stress and four different types of drought stress conditions. The relationship of genotypic variation in yield under drought conditions to genetic yield potential, flowering time and flowering delay, and to a drought response index (DRI) that removed the effect of potential yield and flowering time on yield under stress was examined. Drought stress that developed prior to flowering generally delayed the time of flowering of genotypes, and the delay in flowering was negatively associated with grain yield, fertile panicle percentage and filled grain percentage. Genotypes with a longer delay in flowering time had extracted more water during the early drought period, and as a consequence, had higher water deficits. They were consistently associated with a larger yield reduction under drought and in one experiment with a smaller DRI. Genotypes, however, responded differently to the different drought stress conditions and there was no consistency in the DRI estimates for the different genotypes across the drought stress experiments. The results indicate that with the use of irrigated-control and drought test environments, genotypes with drought resistance can be identified by using DRI or delay in flowering. However, selections will differ depending on the type of drought condition. The inconsistency of the estimates in DRI and flowering delay across different drought conditions reflects the nature of the large genotype-by-environment interactions observed for grain yield under various types of drought in rainfed lowland conditions. (C), 2002 Elsevier Science B.V. All rights reserved.

Evaluation of various pre-treatments for the dehydration of banana and selection of suitable drying models

The thin-layer drying behaviour of bananas in a beat pump dehumidifier dryer was examined. Four pre-treatments (blanching, chilling, freezing and combined blanching and freezing) were applied to the bananas, which were dried at 50 degreesC with an air velocity of 3.1 m s(-1) and with the relative humidity of the inlet air of 10-35%. Three drying models, the simple model, the two-term exponential model and the Page model were examined. All models were evaluated using three statistical measures, correlation coefficient, root means square error, and mean absolute percent error. Moisture diffusivity was calculated based on the diffusion equation for an infinite cylindrical shape using the slope method. The rate of drying was higher for the pre-treatments involving freezing. The sample which was blanched only did not show any improvement in drying rate. In fact, a longer drying time resulted due to water absorption during blanching. There was no change in the rate for the chilled sample compared with the control. While all models closely fitted the drying data, the simple model showed greatest deviation from the experimental results. The two-term exponential model was found to be the best model for describing the drying curves of bananas because its parameters represent better the physical characteristics of the drying process. Moisture diffusivities of bananas were in the range 4.3-13.2 x 10(-10) m(2)s(-1). (C) 2002 Published by Elsevier Science Ltd.

Does primary medical practitioner involvement with a specialist team improve patient outcomes? A systematic review.

Patients with chronic or complex medical or psychiatric conditions are treated by many practitioners, including general practitioners (GPs). Formal liaison between primary and specialist is often assumed to offer benefits to patients The aim of this study was to assess the efficacy of formal liaison of GPs with specialist service providers on patient health outcomes, by conducting a systematic review of the published literature in MEDLINE, EMBASE, PsychINFO, CINAHL and Cochrane Library databases using the following search terms family physicians': synonyms of 'patient care planning', 'patient discharge' and 'patient care team'; and synonyms of 'randomised controlled trials'. Seven studies were identified, involving 963 subjects and 899 controls. most health outcomes were unchanged, although some physical and functional health outcomes were improved by formal liaison between GPs and specialist services, particularly among chronic mental illness patients. Some health outcomes worsened during the intervention. Patient retention rates within treatment programmes improved with GP involvement, as did patient satisfaction. Doctor (GP and specialist) behaviour changed, with reports of more rational use of resources and diagnostic tests, improved clinical skills, more frequent use of appropriate treatment strategies, and more frequent clinical behaviours designed to detect disease complications Cost effectiveness could not be determined. In conclusion, formal liaison between GPs and specialist services leaves most physical health outcomes unchanged, but improves functional outcomes in chronically mentally ill patients. It may confer modest long-term health benefits through improvements in patient concordance with treatment programmes and more effective clinical practice.

A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.

Carbamazepine augmentation for schizophrenia: How good is the evidence?

Background: Augmentation strategies in schizophrenia treatment remain an important issue because despite the introduction of several new antipsychotics, many patients remain treatment resistant. The aim of this study was to undertake a systematic review and meta-analysis of the safety and efficacy of one frequently used adjunctive compound: carbamazepine. Data sources and study selection: Randomized controlled trials comparing carbamazopine (as a sole or as an adjunctive compound) with placebo or no intervention in participants with schizophrenia or schizoaffective disorder were searched for by accessing 7 electronic databases, cross-referencing publications cited in pertinent studies, and contacting drug companies that manufacture carbamazepine. Method: The identified studies were independently inspected and their quality assessed by 2 reviewers, Because the study results were generally incompletely reported, original patient data were requested from the authors; data were received for 8 of the 10 randomized controlled trials included in the present analysis, allowing for a reanalysis of the primary data. Dichotomous variables were analyzed using the Mantel-Haenszel odds ratio and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. Results: Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. Conclusion: At present, this augmentation strategy cannot be recommended for routine use. The most promising targets for future trials are patients with excitement, aggression, and schizoaffective disorder bipolar type.

Genetic constraints on the evolution of mate recognition under natural selection

Field populations of Drosophila serrata display reproductive character displacement in cuticular hydrocarbons (CHCs) when sympatric with Drosophila birchii. We have previously shown that the naturally occurring pattern of reproductive character displacement can be experimentally replicated by exposing field allopatric populations of D. serrata to experimental sympatry with D. birchii. Here, we tested whether the repeated evolution of reproductive character displacement in natural and experimental populations was a consequence of genetic constraints on the evolution of CHCs. The genetic variance-covariance (G) matrices for CHCs were determined for populations of D. serrata that had evolved in either the presence or absence of D. birchii under field and experimental conditions. Natural selection on mate recognition under both field and experimental sympatric conditions increased the genetic variance in CHCs consistent with a response to selection based on rare alleles. A close association between G eigenstructure and the eigenstructure of the phenotypic divergence (D) matrix in natural and experimental populations suggested that G matrix eigenstructure may have determined the direction in which reproductive character displacement evolved during the reinforcement of mate recognition.