Current concepts in central nervous system regeneration

A dictum long-held has stated that the adult mammalian brain and spinal cord are not capable of regeneration after injury. Recent discoveries have, however, challenged this dogma. In particular, a more complete understanding of developmental neurobiology has provided an insight into possible ways in which neuronal regeneration in the central nervous system may be encouraged. Knowledge of the role of neurotrophic factors has provided one set of strategies which may be useful in enhancing CNS regeneration. These factors can now even be delivered to injury sites by transplantation of genetically modified cells. Another strategy showing great promise is the discovery and isolation of neural stem cells from adult CNS tissue. It may become possible to grow such cells in the laboratory and use these to replace injured or dead neurons. The biological and cellular basis of neural injury is of special importance to neurosurgery, particularly as therapeutic options to treat a variety of CNS diseases becomes greater. (C) 2002 Published by Elsevier Science Ltd.

Development of a generic crop model template in the cropping system model APSIM

The Agricultural Production Systems slMulator, APSIM, is a cropping system modelling environment that simulates the dynamics of soil-plant-management interactions within a single crop or a cropping system. Adaptation of previously developed crop models has resulted in multiple crop modules in APSIM, which have low scientific transparency and code efficiency. A generic crop model template (GCROP) has been developed to capture unifying physiological principles across crops (plant types) and to provide modular and efficient code for crop modelling. It comprises a standard crop interface to the APSIM engine, a generic crop model structure, a crop process library, and well-structured crop parameter files. The process library contains the major science underpinning the crop models and incorporates generic routines based on physiological principles for growth and development processes that are common across crops. It allows APSIM to simulate different crops using the same set of computer code. The generic model structure and parameter files provide an easy way to test, modify, exchange and compare modelling approaches at process level without necessitating changes in the code. The standard interface generalises the model inputs and outputs, and utilises a standard protocol to communicate with other APSIM modules through the APSIM engine. The crop template serves as a convenient means to test new insights and compare approaches to component modelling, while maintaining a focus on predictive capability. This paper describes and discusses the scientific basis, the design, implementation and future development of the crop template in APSIM. On this basis, we argue that the combination of good software engineering with sound crop science can enhance the rate of advance in crop modelling. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Lipoamino acid-based adjuvant carrier system: Enhanced immunogenicity of group a streptococcal peptide epitopes

Lipoamino acid-based synthetic peptides (lipid core peptides, LCP) derived from the type-specific and conserved region determinants of group A streptococci (GAS) were evaluated as potential candidate sequences in a vaccine to prevent GAS-associated diseases, including rheumatic heart, disease and poststreptococcal acute glomerulonephritis. The LCP peptides had significantly enhanced immunogenicity as compared with the monomeric peptide epitopes. Furthermore, the peptides incorporated into the LCP system generated epitope-specific antibodies without the use of any conventional adjuvant.

Control of Aedes vectors of dengue in three provinces of Vietnam by use of Mesocyclops (Copepoda) and community-based methods validated by entomologic, clinical, and serological surveillance

We describe remarkable success in controlling dengue vectors, Aedes aegypti (L.) and Aedes albopictus (Skuse), in 6 communes with 11,675 households and 49,647 people in the northern provinces of Haiphong, Hung Yen, and Nam Dinh in Vietnam. The communes were selected for high-frequency use of large outdoor concrete tanks and wells. These were found to be the source of 49.6-98.4% of Ae. aegypti larvae, which were amenable to treatment with local Mesocyclops, mainly M. woutersi Van der Velde, M. aspericornis (Daday) and M. thermocyclopoides Harada. Knowledge, attitude, and practice surveys were performed to determine whether the communities viewed dengue and dengue hemorrhagic fever as a serious health threat; to determine their knowledge of the etiology, attitudes, and practices regarding control methods including Mesocyclops; and to determine their receptivity to various information methods. On the basis of the knowledge, attitude, and practice data, the community-based dengue control program comprised a system of local leaders, health volunteer teachers, and schoolchildren, supported by health professionals. Recycling of discards for economic gain was enhanced, where appropriate, and this, plus 37 clean-up campaigns, removed small containers unsuitable for Mesocyclops treatment. A previously successful eradication at Phan Boi village (Hung Yen province) was extended to 7 other villages forming Di Su commune (1,750 households) in the current study. Complete control was also achieved in Nghia Hiep (Hung Yen province) and in Xuan Phong (Nam Dinh province); control efficacy was greater than or equal to 99.7% in the other 3 communes (Lac Vien in Haiphong, Nghia Dong, and Xuan Kien in Nam Dinh). Although tanks and wells were the key container types of Ae. aegypti productivity, discarded materials were the source of 51% of the standing crop of Ae. albopictus. Aedes albopictus larvae were eliminated from the 3 Nam Dinh communes, and 86-98% control was achieved in the other 3 communes. Variable dengue attack rates made the clinical and serological comparison of control and untreated communes problematic, but these data indicate that clinical surveillance by itself is inadequate to monitor dengue transmission.

The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system

Clinical trials have established bosentan, an orally active non-selective endothelin (ET) receptor antagonist, as a beneficial treatment in pulmonary hypertension. Trials have also shown short-term benefits of bosentan in systemic hypertension and congestive heart failure. However, bosentan also increased plasma levels of ET-1, probably by inhibiting the clearance of ET-1 by endothelin type B (ET.) receptors, and this may mean its effectiveness is reduced with long-term clinical use. Preliminary data suggests that selective endothelin type A (ETA) receptor antagonists (BQ-123, sitaxsentan) may be more beneficial than the non-selective ET receptor antagonists in heart failure, especially when the failure is associated with pulmonary hypertension. Experimental evidence in animal disease models suggests that non-selective ET or selective ETA receptor antagonism may have a role in the treatment of athero-sclerosis, restenosis, myocarditis, shock and portal hypertension. In animal models of myocardial infarction and/or reperfusion injury, non-selective ET or selective ETA receptor antagonists have beneficial or detrimental effects depending on the conditions and agents used. Thus clinical trials of the nonselective ET or selective ETA receptor antagonists in these conditions are not presently warranted. Several selective endothelin-converting enzyme inhibitors tors have been synthesised recently, and these are only beginning to be tested in animal models of cardiovascular disease, and thus the clinical potential of these inhibitors is still to be defined.

Use of heterologously-expressed cytochomre P450 and glutathione transferase enzymes in toxicity assays

Our groups have had a long-term interest in utilizing bacterial systems in the characterization of bioactivation and detoxication reactions catalyzed by cytochrome P450 (P450) and glutathione transferase (GST) enzymes. Bacterial systems remain the first choice for initial screens with new chemicals and have advantages, including high-throughput capability. Most human P450s of interest in toxicology have been readily expressed in Escherichia coli with only minor sequence modification. These enzymes can be readily purified and used in assays of activation of chemicals. Bicistronic systems have been developed in order to provide the auxiliary NADPH-P450 reductase. Alternative systems involve these enzymes expressed together within bacteria. In one approach, a lac selection system is used with E. coli and has been applied to the characterization of inhibitors of P450s 1A2 and 1131, as well as in basic studies involving random mutagenesis. Another approach utilizes induction of the SOS (umu) response in Salmonella typhimurium, and systems have now been developed with human P450s 1A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4, which have been used to report responses from heterocyclic amines. S. typhimurium his reporter systems have also been used with GSTs, first to demonstrate the role of rat GST 5-5 in the activation of dihalomethanes. These systems have been used to compare these GSTs with regard to activation of dihaloalkanes and potential toxicity. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Measuring range of active cervical rotation in a position of full head flexion using the 3D Fastrak measurement system: an intra-tester reliability study

Most external assessments of cervical range of motion assess the upper and lower cervical regions simultaneously. This study investigated the within and between days reliability of the clinical method used to bias this movement to the upper cervical region, namely measuring rotation of the head and neck in a position of full cervical flexion. Measurements were made using the Fastrak measurement system and were conducted by one operator. Results indicated high levels of within and between days repeatability (range of ICC2,1 values: 0.85-0.95). The ranges of axial rotation to right and left, measured with the neck positioned in full flexion, were approximately 56% and 50%, respectively of total cervical rotation, which relates well to the proportional division of rotation in the upper and lower cervical regions. These results suggest that this method of measuring rotation would be appropriate for use in subject studies where movement dysfunction is present in the upper cervical region, such as those with cervicogenic headache. (C) 2003 Elsevier Science Ltd. All rights reserved.

Movements of the ricefield rat, Rattus argentiventer, near a trap-barrier system in rice crops in West Java, Indonesia

The movements of the ricefield rats (Rattus argentiventer) near a trap-barrier system (TBS) were assessed in lowland flood-irrigated rice crops in West Java, Indonesia, to test the hypothesis that a TBS with a 'trap-crop' modifies the movements of rats within 200 m from the trap-crop. The home range use and locations of rat burrows were assessed using radiotelemetry at two sites, one with a TBS with trap-crop (Treatment site, the crop inside the fence was planted 3 weeks earlier than the surrounding crop) and the other with a TBS without trap-crop (Control site, the crop inside the fence was planted at the same time as the surrounding crop). Each TBS was a 50 x 50 m plastic fence with eight multiple-capture rat traps set at the base. More than 700 rats were caught in the TBS with trap-crop, whereas only 10 rats were caught in the TBS without trap-crop. The home range size of females was significantly smaller at the Treatment site (0.96 ha) than the Control site (2.99 ha), but there was no difference for males. Seventy-eight per cent of rats caught in the TBS and fitted with radiocollars had their daytime burrow locations within 200 m of the TBS. We could not determine if the rats caught in the TBS were residents or transients according to demographic parameters. Our results support the hypothesis that a TBS with a trap-crop protects the surrounding rice crop out to a distance of at least 200 m.

A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system

Objectives: The aim was to determine whether methadone maintenance treatment reduced heroin use, syringe sharing and HIV or hepatitis C incidence among prisoners. Methods: All eligible prisoners seeking drug treatment were randomised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months. Heroin use was measured by hair analysis and self report; drugs used and injected and syringe sharing were measured by self report. Hepatitis C and HIV incidence was measured by serology. Results: Of 593 eligible prisoners, 382 (64%) were randomised to MMT (n = 191) or control (n = 191). 129 treated and 124 control subjects were followed up at 5 months. Heroin use was significantly lower among treated than control subjects at follow up. Treated subjects reported lower levels of drug injection and syringe sharing at follow up. There was no difference in HIV or hepatitis C incidence. Conclusions: Consideration should be given to the introduction of prison methadone programs particular where community based programs exist. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Prediction of mortality in patients without angina: Use of an exercise score and exercise echocardiography

Background Exercise testing has limited efficacy for identifying coronary artery disease (CAD) in the absence of anginal. symptoms. Exercise echocardiography is more accurate than standard exercise testing, but its efficacy in this situation has not been defined. We sought to identify whether the Duke treadmill. score or exercise echocardiography (ExE) could be used to identify risk in patients without anginal symptoms. Methods We studied 1859 patients without typical or atypical angina, heart failure, or a history or ECG evidence of infarction or CAD, who were referred for ExE, of whom 1832 (age 51 15 years, 944 men) were followed for up to 10 years. The presence and extent of ischaemia and scar were interpreted by expert reviewers at the time of the original study. Results Exercise provoked significant (>0.1 mV) ST segment depression in 215 patients (12%), and wall motion abnormalities in 137 (8%). Seventy-eight patients (4%) died before revascularization, only 17 from known cardiac causes. The independent predictors of death were age (RR 1.1, p

Integrated control of nitrate recirculation and external carbon addition in a predenitrification system

The integrated control of nitrate recirculation and external carbon addition in a predenitrification biological wastewater treatment system is studied. The proposed control structure consists of four feedback control loops, which manipulate the nitrate recirculation and the carbon dosage flows in a highly coordinated manner such that the consumption of external carbon is minimised while the nitrate discharge limits (based on both grab and composite samples) are met. The control system requires the measurement of the nitrate concentrations at the end of both the anoxic and the aerobic zones. Distinct from ordinary control systems, which typically minimise the variation in the controlled variables, the proposed control system essentially maximises the diurnal variation of the effluent nitrate concentration and through this maximises the use of influent COD for denitrification, thus minimising the requirement for external carbon source. Simulation studies using a commonly accepted simulation benchmark show that the controlled system consistently achieves the designated effluent quality with minimum costs.

The use of 16s rDNA restriction fragment length polymorphism analysis for the identification of non-fermenting gram negative bacilli in a cystic fibrosis microbiology referral service

The utility of 16s rDNA restriction fragment length polymorphism (RFLP) analysis for the partial genomovar differentiation of Burkholderia cepacia complex bacterium is well documented. We compared the 16s rDNA RFLP signatures for a number of non-fermenting gram negative bacilli (NF GNB) LMG control strains and clinical isolates pertaining to the genera Burkholderia, Pseudomonas, Achromobacter (Alcaligenes), Ralstonia, Stenotrophomonas and Pandoraea. A collection of 24 control strain (LMG) and 25 clinical isolates were included in the study. Using conventional PCR, a 1.2 kbp 16s rDNA fragment was generated for each organism. Following restriction digestion and electrophoresis, each clinical isolate RFLP signature was compared to those of the control strain panel. Nineteen different RFLP signatures were detected from the 28 control strains included in the study. TwentyoneyTwenty- five of the clinical isolates could be classified by RFLP analysis into a single genus and species when compared to the patterns produced by the control strain panel. Four clinical B. pseudomallei isolates produced RFLP signatures which were indistinguishable from B. cepacia genomovars I, III and VIII. The identity of these four isolates were confirmed using B. pseudomallei specific PCR. 16s rDNA RFLP analysis can be a useful identification strategy when applied to NF GNB, particularly for those which exhibit colistin sulfate resistance. The use of this molecular based methodology has proved very useful in the setting of a CF referral laboratory particularly when utilised in conjunction with B. cepacia complex and genomovar specific PCR techniques. Species specific PCR or sequence analysis should be considered for selected isolates; especially where discrepancies between epidemiology, phenotypic and genotypic characteristics occur.

Use of confocal scanning laser microscopy to measure the concentrations of aerial and penetrative hyphae during growth of Rhizopus oligosporus on a solid surface

In order to develop a method for use in investigations of spatial biomass distribution in solid-state fermentation systems, confocal scanning laser microscopy was used to determine the concentrations of aerial and penetrative biomass against height and depth above and below the substrate surface, during growth of Rhizopus oligosporus on potato dextrose agar. Penetrative hyphae had penetrated to a depth of 0.445 cm by 64 h and showed rhizoid morphology, in which the maximum biomass concentration, of 4.45 mg dry wt cm(-3), occurred at a depth of 0.075 cm. For aerial biomass the maximum density of 39.54 mg dry wt(-3) occurred at the substrate surface. For both aerial and penetrative biomass, there were two distinct regions in which the biomass concentration decayed exponentially with distance from the surface. For aerial biomass, the first exponential decay region was up to 0.1 cm height. The second region above the height of 0.1 cm corresponded to that in which sporangiophores dominated. This work lays the foundation for deeper studies into what controls the growth of fungal hyphae above and below the surfaces of solid substrates. (C) Wiley Periodicals, Inc.

Modified logit life table system: Principles, empirical validation, and application

Despite its widespread use, the Coale-Demeny model life table system does not capture the extensive variation in age-specific mortality patterns observed in contemporary populations, particularly those of the countries of Eastern Europe and populations affected by HIV/AIDS. Although relational mortality models, such as the Brass logit system, can identify these variations, these models show systematic bias in their predictive ability as mortality levels depart from the standard. We propose a modification of the two-parameter Brass relational model. The modified model incorporates two additional age-specific correction factors (gamma(x), and theta(x)) based on mortality levels among children and adults, relative to the standard. Tests of predictive validity show deviations in age-specific mortality rates predicted by the proposed system to be 30-50 per cent lower than those predicted by the Coale-Demeny system and 15-40 per cent lower than those predicted using the original Brass system. The modified logit system is a two-parameter system, parameterized using values of l(5) and l(60).