The application of statistical process control charts to the detection and monitoring of hospital-acquired infections

The monitoring of infection control indicators including hospital-acquired infections is an established part of quality maintenance programmes in many health-care facilities. However, surveillance data use can be frustrated by the infrequent nature of many infections. Traditional methods of analysis often provide delayed identification of increasing infection occurrence, placing patients at preventable risk. The application of Shewhart, Cumulative Sum (CUSUM) and Exponentially Weighted Moving Average (EWMA) statistical process control charts to the monitoring of indicator infections allows continuous real-time assessment. The Shewhart chart will detect large changes, while CUSUM and EWMA methods are more suited to recognition of small to moderate sustained change. When used together, Shewhart and EWMA methods are ideal for monitoring bacteraemia and multiresistant organism rates. Shewhart and CUSUM charts are suitable for surgical infection surveillance.

Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo

The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal robes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.

Vps45p stabilizes the syntaxin homologue Tlg2p and positively regulates SNARE complex formation

Sec1p-like/Munc-18 (SM) proteins bind to t-SNAREs and inhibit ternary complex formation. Paradoxically, the absence of SM proteins does not result in constitutive membrane fusion, Here, we show that in yeast cells lacking the SM protein Vps45p, the t-SNARE Tlg2p is down-regulated, to undetectable levels, by rapid proteasomal degradation. In the absence of Vps45p, Tlg2p can be stabilized through abolition of proteasome activity. Surprisingly, the stabilized Tlg2p was targeted to the correct intracellular location. However, the stabilized Tlg2p is non-functional and unable to bind its cognate SNARE binding partners, Tlg1p and Vti1p, in the absence of Vps45p, A truncation mutant lacking the first 230 residues of Tlg2p no longer bound Vps45p but was able to form complexes with Tlg1p and Vti1p in the absence of the SM protein. These data provide us with two valuable insights into the function of SM proteins. First, SM proteins act as chaperone-like molecules for their cognate t-SNAREs, Secondly, SM proteins play an essential role in the activation process allowing their cognate t-SNARE to participate in ternary complex formation.

Inorganic nitrogen requirements during shoot organogenesis in tobacco leaf discs

The role of nitrate, ammonium, and culture medium pH on shoot organogenesis in Nicotiana tabacum zz100 leaf discs was examined. The nitrogen composition of a basal liquid shoot induction medium (SIM) containing 39.4 mM NO3- and 20.6 mM NH4+ was altered whilst maintaining the overall ionic balance with Na+ and Cl- ions. Omission of total nitrogen and nitrate, but not ammonium, from SIM prevented the initiation and formation of shoots. When nitrate was used as the sole source of nitrogen, a high frequency of explants initiated and produced leafy shoots. However, the numbers of shoots produced were significantly fewer than the control SIM. Buffering nitrate-only media with the organic acid 2[N-morpholinol]thanesulphonic acid (MES) could not compensate for the omission of ammonium. Ammonium used as the sole source of nitrogen appeared to have a negative effect on explant growth and morphogenesis, with a significant lowering of media pH. Buffering ammonium-only media with MES stabilized pH and allowed a low frequency of explants to initiate shoot meristems. However, no further differentiation into leafy shoots was observed. The amount of available nitrogen appears to be less important than the ratio between nitrate and ammonium. Shoot formation was achieved with a wide range of ratios, but media containing 40 mM nitrate and 20 mM ammonium (70:30) produced the greatest number of shoots per explant. Results from this study indicate a synergistic effect between ammonium and nitrate on shoot organogenesis independent of culture medium pH.

Sludge population optimisation: a new dimension for the control of biological wastewater treatment systems

The activated sludge comprises a complex microbiological community. The structure (what types of microorganisms are present) and function (what can the organisms do and at what rates) of this community are determined by external physico -chemical features and by the influent to the sewage treatment plant. The external features we can manipulate but rarely the influent. Conventional control and operational strategies optimise activated sludge processes more as a chemical system than as a biological one. While optimising the process in a short time period, these strategies may deteriorate the long-term performance of the process due to their potentially adverse impact on the microbial properties. Through briefly reviewing the evidence available in the literature that plant design and operation affect both the structure and function of the microbial community in activated sludge, we propose to add sludge population optimisation as a new dimension to the control of biological wastewater treatment systems. We stress that optimising the microbial community structure and property should be an explicit aim for the design and operation of a treatment plant. The major limitations to sludge population optimisation revolve around inadequate microbiological data, specifically community structure, function and kinetic data. However, molecular microbiological methods that strive to provide that data are being developed rapidly. The combination of these methods with the conventional approaches for kinetic study is briefly discussed. The most pressing research questions pertaining to sludge population optimisation are outlined. (C) 2002 Elsevier Science Ltd. All rights reserved.

Destructive periodontitis lesions are determined by the nature of the lymphocytic response

It is now 35 years since Brandtzaeg and Kraus (1965) published their seminal work entitled Autoimmunity and periodontal disease. Initially, this work led to the concept that destructive periodontitis was a localized hypersensitivity reaction involving immune complex formation within the tissues. In 1970, Ivanyi and Lehner highlighted a possible role for cell-mediated immunity, which stimulated a flurry of activity centered on the role of lymphokines such as osteoclast-activating factor (OAF), macrophage-activating factor (MAF), macrophage migration inhibition factor (MIF), and myriad others. In the late 1970s and early 1980s, attention focused on the role of polymorphonuclear neutrophils, and it was thought that periodontal destruction occurred as a series of acute exacerbations. As well, at this stage doubt was being cast on the concept that there was a neutrophil chemotactic defect in periodontitis patients. Once it was realized that neutrophils were primarily protective and that severe periodontal destruction occurred in the absence of these cells, attention swung back to the role of lymphocytes and in particular the regulatory role of T-cells. By this time in the early 1990s, while the roles of interleukin (IL)-1, prostaglandin (PG) E-2, and metalloproteinases as the destructive mediators in periodontal disease were largely understood, the control and regulation of these cytokines remained controversial. With the widespread acceptance of the Th1/Th2 paradigm, the regulatory role of T-cells became the main focus of attention, Two apparently conflicting theories have emerged. One is based on direct observations of human lesions, while the other is based on animal model experiments and the inability to demonstrate IL-4 mRNA in gingival extracts. As part of the Controversy series, this review is intended to stimulate debate and hence may appear in some places provocative. In this context, this review will present the case that destructive periodontitis is due to the nature of the lymphocytic infiltrate and is not due to periodic acute exacerbations, nor is it due to the so-called virulence factors of putative periodontal pathogens.

Cost of malaria control in China: Henan's consolidation programme from community and government perspectives

Objective To assist with strategic planning for the eradication,of malaria in Henan Province, China, which reached the consolidation phase of malaria control in 1992, when only 318 malaria cases were reported, Methods We conducted a prospective two-year study of the costs for Henan's malaria control programme. We used a cost model that could also be applied to other malaria programmes in-mainland China, and analysed the cost of the three components of Henan's malaria programme. suspected malaria case management,, vector surveillance,,and population blood surveys. Primary cost data were collected from the government, and data on suspected malaria patient's were collected in two malaria counties (population 2 093 100). We enlisted the help of 260 village doctors. in six-townships or former communities (population 247 762), and studied all 12 315 reported cases of suspected malaria in catchment areas in 1994 and 1995. Findings The average-annual government investment in malaria control was estimated to be US$ 111 516 (case-management 59%; active blood surveys 25%;vector surveillance 12%; and contingencies and special projects 4%). The average cost (direct and indirect) for-patients seeking-treatment for suspected malaria was US$ 3.48, equivalent,to 10 days' income for rural residents. Each suspected malaria case cost the government an, average of US$ 0.78. Conclusion Further cuts in government funding will increase future costs, when epidemic malaria returns; investment in malaria control should therefore continue at least at current levels,of US$ 0.03 per person a risk.

Complementation analysis of the flavivirus Kunjin NS3 and NS5 proteins defines the minimal regions essential for formation of a replication complex and shows a requirement of NS3 in cis for virus assembly

We have previously reported successful trans-complementation of defective Kunjin virus genomic RNAs with a range of large lethal deletions in the nonstructural genes NSI, NS3, and NS5 (A. A. Khromykh et al., J. Virol. 74:3253-3263, 2000). In this study we have mapped further the minimal region in the NS5 gene essential for efficient trans-complementation of genome-length RNAs in repBHK cells to the first 316 of the 905 codons. To allow amplification and easy detection of complemented defective RNAs with deletions apparently affecting virus assembly, we have developed a dual replicon complementation system. In this system defective replicon RNAs with a deletion(s) in the nonstructural genes also encoded the puromycin resistance gene (PAC gene) and the reporter gene for beta-galactosidase (beta-Gal). Complementation of these defective replicon RNAs in repBHK cells resulted in expression of PAC and beta-Gal which allowed establishment of cell lines stably producing replicating defective RNAs by selection with puromycin and comparison of replication efficiencies of complemented defective RNAs by beta-Gal assay. Using this system we demonstrated that deletions in the C-terminal 434 codons of NS3 (codons 178 to 611) were complemented for RNA replication, while any deletions in the first 178 codons were not. None of the genome-length RNAs containing deletions in NS3 shown to be complementable for RNA replication produced secreted defective viruses during complementation in repBHK cells. In contrast, structural proteins produced from these complemented defective RNAs were able to package helper replicon RNA. The results define minimal regions in the NS3 and NS5 genes essential for the formation of complementable replication complex and show a requirement of NS3 in cis for virus assembly.

Mango stem-end rot (Botryosphaeria dothidea) disease control by partial-pressure infiltration of fungicides

The in vitro efficacy of several fungicides against Botryosphaeria dothidea (syn. Dothiorella dominicana) and their in vivo efficacy in controlling mango cv. Kensington Pride stem-end rot on partial-pressure infiltration v. dip treatment of green mature fruit was evaluated. In vitro sensitivity of B. dothidea to Benlate (benomyl), Sportak (prochloraz) and Scala (pyrimethanil) at 10 dilutions of the manufacturer's recommended rate was first determined at typical cold (13degreesC) and shelf (23degreesC) storage temperatures. The effectiveness of partial-pressure infiltration and conventional hot (52degreesC) or cold (26degreesC) dipping of fruit after harvest was then evaluated using the commercially recommended rate for each fungicide. In vitro, Benlate and Sportak prevented the growth of B. dothidea at both storage temperatures and at all concentrations, while Scala partially controlled growth of the pathogen. Benlate was the most effective fungicide for stem-end rot control. Sportak and Scala resulted in stem-end rot control when applied by partial-pressure infiltration, but not as dips. Partial-pressure infiltration holds promise for enhancing the efficacy of otherwise less effective but alternative fungicides for control of stem-end rot diseases.

Melanoma in adolescents: A case-control study of risk factors in Queensland, Australia

The incidence of melanoma increases markedly in the second decade of life but almost nothing is known of the causes of melanoma in this age group. We report on the first population-based case-control study of risk factors for melanoma in adolescents (15-19 years). Data were collected through personal interviews with cases, controls and parents. A single examiner conducted full-body nevus counts and blood samples were collected from cases for analysis of the CDKN2A melanoma predisposition gene. A total of 201 (80%) of the 250 adolescents with melanoma diagnosed between 1987 and 1994 and registered with the Queensland Cancer Registry and 205 (79%) of 258 age-, gender- and location-matched controls who were contacted agreed to participate. The strongest risk factor associated with melanoma in adolescents in a multivariate model was the presence of more than 100 nevi 2 mm or more in diameter (odds ratio [OR] = 46.5, 95% confidence interval [Cl] = 11.4-190.8). Other risk factors were red hair (OR = 5.4, 95%Cl = 1.0-28.4); blue eyes (OR = 4.5, 95%Cl = 1.5- 13.6); inability to tan after prolonged sun exposure (OR = 4.7, 95%Cl = 0.9-24.6); heavy facial freckling (OR = 3.2, 95% Cl = 0.9-12.3); and family history of melanoma (OR = 4.0, 95%Cl = 0.8-18.9). Only 2 of 147 cases tested had germline variants or mutations in CDKN2A. There was no association with sunscreen use overall, however, never/rare use of sunscreen at home under the age of 5 years was associated with increased risk (OR = 2.2, 95%Cl = 0.7-7.1). There was no difference between cases and controls in cumulative sun exposure in this high-exposure environment. Factors indicating genetic susceptibility to melanoma, in particular, the propensity to develop nevi and freckles, red hair, blue eyes, inability to tan and a family history of the disease are the primary determinants of melanoma among adolescents in this high solar radiation environment. Lack of association with reported sun exposure is consistent with the high genetic susceptibility in this group. (C) 2002 Wiley-Liss, Inc.

Dental erosion in asthma: A case-control study from south east Queensland

Background: Asthma medication places patients at risk of dental erosion by reducing salivary protection against extrinsic or intrinsic acids. But patterns of lesions in asthmatics may differ from patterns in non-asthmatics, because gastro-oesophageal reflux (GOR) is found in 60 per cent of asthmatics. Methods: The lesions in 44 asthma cases were compared to those of age and sex match controls with no history of asthma or medications drawn from the dental records of 423 patients referred concerning excessive tooth wear. The subjects were 70 males age range 15 to 55 years and 18 females age range 18 to 45. Anamnestic clinical data were compared between the two groups. Models of all 88 subjects were examined by light microscopy, and wear patterns were recorded on permanent central incisor, canine, premolar and first molar teeth. Results: Clinical differences were a higher incidence of tooth hypersensitivity; xerostomia, salivary gland abnormalities, gastric complaints, and self induced vomiting in the cases. No differences were found between the cases and controls on citrus fruit and acid soft drink consumption. More occlusal erosion sites were found in cases, whereas more attrition sites were found in the controls. There were no significant differences in palatal erosion on maxillary anterior teeth found between cases and controls. Lingual erosion of the mandibular incisors, found only in GOR patients, was not observed. Conclusions: A higher incidence of erosion was found in asthmatics. Gastro-oesophageal reflux symptoms were not associated with the sign of lingual mandibular incisor erosion. The clinical significance is that asthmatics are at risk of dental erosion from extrinsic acid, but GOR does not appear to contribute in a site-specific manner.