Management gaps analysis: a case study of groundwater resource management in New Zealand

The primary objective of this project is to identify gaps, whether real or perceived, that hinder effective groundwater management in New Zealand. These gaps show as gaps in information, gaps in implementation, gaps in technological and management tools, and gaps in understanding of fundamental processes. The secondary objective is to propose a management strategy to close the identified gaps. Several methods are used to meet these objectives: surveys distributed to selected staff in each regional council; the review of various written reports; the analysis of land-use databases; and private consultation within each regional council. Results show that groundwater management in New Zealand is generally reactionary with the main gaps being in strategic planning and national guidelines. Most gaps appear to be predominantly information and implementation issues. In some cases there are gaps in the understanding of fundamental processes within an aquifer system, including the long-term effects of land-use on groundwater quality. An adaptive management approach is suggested as a means of closing these gaps.     

Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.     

Sacrospinous colpopexy in the management of uterovaginal prolapse

The tet(M) genes were characterized from 84 isolates of 10 different bacterial species isolated from the periodontal pockets of 16 patients with periodontal disease. A 740 bp polymerase chain reaction product from the hypervariable region of the tet(M) structural gene was cleaved with the restriction enzymes AluI and HinfI. Three different restriction patterns were identified for each of the two enzymes. By DNA sequencing, using a direct solid-phase automated sequencing method, the isolates could be grouped into 3 different clusters of tet(M) subtypes. The internal DNA homology within each subtype was 98-100%; the homology between clusters was 89-94%. Two different subtypes were identified in 9 of 10 bacterial species, and the remaining species had 3 different subtypes. One of the subtypes (M3) was seen mainly in the anaerobic isolates. This subtype was different from all earlier sequenced structural tet(M) genes present in the Genbank. Most patients had two different subtypes of tet(M), and a third subtype was seen in the 3 patients who exhibited the greatest variety of tetracycline-resistant bacterial species. It appears that the presence of one subtype of the tet(M) gene within a patient or bacterial species does not prevent the acquisition of another subtype of the same gene. This study identified a new subtype of the tet(M) gene and grouped it into 3 distinct yet highly homologous genetic subtypes.     

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase

Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.     

A small-angle X-ray scattering study of powder compaction

This work demonstrated a novel and potentially important application of two-dimensional small-angle X-ray scattering (2D-SAXS) to investigate powder compaction. SAXS from powder compacts of three materials commonly used for pharmaceutical tabletting exhibited azimuthal variations, with stronger intensity in the direction of the applied compaction force, relative to the transverse direction. This implied that compaction of a (macroscopic) powder could also produce changes on the molecular (nanometre) scale, which can be probed by 2D-SAXS. Two possible explanations for this effect were suggested. A combination of anisometric (i.e. elongated or flattened) granules with anisotropic morphologies could result in azimuthal variation in X-ray scattering due to granule orientation. It is expected that this mechanism would require relatively low packing density, so may operate during die filling. Granule re-orientation appeared less likely at higher packing densities and compaction pressures, however. Under these conditions, the changes in the 2D-SAXS patterns would be consistent with the powder granules becoming relatively flattened in the compression direction, with corresponding changes in their nano-scale morphology. The magnitude of this effect was found to vary between the materials used and increased with compaction pressure. This suggested that 2D-SAXS studies could provide useful information on force-transmission within a compressed powder. Further analysis of the data also suggested differences in the compaction mechanisms (i.e. granule re-orientation, deformation or fragmentation) between the materials studied.     

Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.