A quantum magnetic analogue to the critical point of water.

At the liquid-gas phase transition in water, the density has a discontinuity at atmospheric pressure; however, the line of these first-order transitions defined by increasing the applied pressure terminates at the critical point1, a concept ubiquitous in statistical thermodynamics2. In correlated quantum materials, it was predicted3 and then confirmed experimentally4,5 that a critical point terminates the line of Mott metal-insulator transitions, which are also first-order with a discontinuous charge carrier density. In quantum spin systems, continuous quantum phase transitions6 have been controlled by pressure7,8, applied magnetic field9,10 and disorder11, but discontinuous quantum phase transitions have received less attention. The geometrically frustrated quantum antiferromagnet SrCu2(BO3)2 constitutes a near-exact realization of the paradigmatic Shastry-Sutherland model12-14 and displays exotic phenomena including magnetization plateaus15, low-lying bound-state excitations16, anomalous thermodynamics17 and discontinuous quantum phase transitions18,19. Here we control both the pressure and the magnetic field applied to SrCu2(BO3)2 to provide evidence of critical-point physics in a pure spin system. We use high-precision specific-heat measurements to demonstrate that, as in water, the pressure-temperature phase diagram has a first-order transition line that separates phases with different local magnetic energy densities, and that terminates at an Ising critical point. We provide a quantitative explanation of our data using recently developed finite-temperature tensor-network methods17,20-22. These results further our understanding of first-order quantum phase transitions in quantum magnetism, with potential applications in materials where anisotropic spin interactions produce the topological properties23,24 that are useful for spintronic applications.

A novel in vitro wound biofilm model used to evaluate low-frequency ultrasonic-assisted wound debridement.

OBJECTIVE: Bacterial biofilms remain difficult to treat. The biofilm mode of growth enables bacteria to survive antibiotic treatment and the inflammatory reaction. Low-frequency ultrasound has recently been shown to improve healing in a variety of settings. It is hypothesised that ultrasound disrupts the biofilm leaving bacteria more vulnerable to antiseptic or antibiotic treatment. The objective of this study is to develop a realistic model to elucidate the effect of ultrasound on biofilms. METHOD: A novel in vitro wound biofilm model was developed. Biofilms of Staphylococcus aureus were casted in a semi-solid agar gel composed of either tryptic soy broth (TSB) or a wound simulating media (WSM; composed of Bolton broth with blood and plasma), to resemble the non-surface attached aggregates. The model was used to evaluate the antibiofilm effect of an ultrasonic-assisted wound debridement device (UAW) in the presence of saline irrigation and treatment with a polyhexamethylene biguanide (PHMB)-containing antiseptic. Confocal microscopy was used to evaluate the effect of treatments on biofilm disruption and cell viability counting measured the antibacterial effects. RESULTS: Confocal microscopy showed that application of 10 seconds of moderate-intensity UAW could effectively disrupt semi-solid biofilms grown on both media settings. This treatment only had a small effect on the cell viability. A 24-hour treatment with PHMB was able to reduce the number of bacteria but not eradicate the biofilm in both media settings. Interestingly, the efficacy of the PHMB antiseptic was significantly higher when applied on biofilms grown in the more complex WSM media. However, we found a significant improvement in reducing the number of viable bacteria grown on both media when applying UAW before administration of the PHMB solution. Applying UAW in the presence of PHMB further improved the efficacy. CONCLUSION: Using a realistic in vitro biofilm wound model, we show combining UAW with a PHMB-containing antiseptic has potential as an antibiofilm strategy in wound care. DECLARATION OF INTEREST: The manufacturer of the ultrasonic-assisted wound debridement device, Söring GmbH, Germany, has supported the ultrasound studies. The funding company had no role in the design, data collection, analysis, review, or approval of the manuscript.

Non-multiresistant and multiresistant methicillin-resistant Staphylococcus aureus in community-acquired infections.

OBJECTIVE: To survey Staphylococcus aureus strains isolated from patients presenting from the community, comparing clinical features and antibiotic sensitivity profiles between multiresistant and non-multiresistant methicillin-resistant and methicillin-sensitive isolates. DESIGN: Retrospective case series. PARTICIPANTS AND SETTING: Patients who presented to emergency or dermatology departments in hospitals served by the South Western Sydney Area Health Service between 1 May 1998 and 30 April 1999. All patients with methicillin-resistant S. aureus (MRSA) and the first 100 with methicillin-sensitive S. aureus were eligible. MAIN OUTCOME MEASURES: Patient demographic characteristics; risk factors; clinical presentation; treatment; outcome; and isolate antibiotic susceptibility. RESULTS: 139 patients were eligible, and 122 had clinical records available. Ten of these 122 (8%) had multiresistant MRSA, 26 (21%) non-multiresistant MRSA and 86 (70%) methicillin-sensitive S. aureus. Among patients with non-multiresistant MRSA, 29% (7/24) were born in New Zealand, Samoa or Tonga, a higher proportion than among those with multiresistant MRSA or methicillin-sensitive S. aureus (P= 0.03). Nearly half (44%) of non-multiresistant MRSA strains were community-acquired in patients with no risk factors. Two-thirds of patients with non-multiresistant MRSA (17/26) presented with cellulitis or abscess, and 58% (11/19 evaluable patients) required surgical treatment. CONCLUSIONS: Non-multiresistant MRSA strains are common, especially among people born in New Zealand, Samoa or Tonga, and are usually community acquired. Medical practitioners should routinely swab all staphylococcal lesions for culture and sensitivity.

Outbreak of echovirus 30 meningitis in Wingecarribee Shire, New South Wales.

An outbreak of aseptic meningitis due to echovirus 30 occurred in the Wingecarribee Shire, NSW, during October to November 1994, with 30 cases fitting the clinical case definition. Cases were ascertained from attendees of the local hospital. Medical files were reviewed and a standard questionnaire administered. Viral cultures were performed on CSF, throat swabs and stool specimens. The clinical presentation and laboratory findings were typical of viral meningitis. Cases were aged 8 months to 51 years; 26 were admitted to hospital. Headache was present in 93%, photophobia in 86%, vomiting in 69%, fever in 72%, and neck stiffness in 62%. In spite of temporal clustering, the mode(s) of transmission in this outbreak remain speculative. Although the route of transmission was not established, general hygiene measures to stop transmission were implemented when a common water source was excluded on epidemiological grounds.

Glucose deprivation induces Akt-dependent synthesis and incorporation of GLUT1, but not of GLUT4, into the plasma membrane of 3T3-L1 adipocytes.

Reduction of the glucose concentration in the culture medium of 3T3-L1 adipose cells below 1.25 mM produces a 4-8-fold stimulation of 2-deoxyglucose uptake which starts after a lag phase of 2 h and is maximal after 10-16 h. In the present study, we employed the 'membrane sheet assay' in order to re-assess the contribution of the transporter isoforms GLUT1 and GLUT4 to this effect. Immunochemical assay of glucose transporters in membranes prepared with the 'sheet assay' revealed that the effect reflected a marked increase of GLUT1 in the plasma membrane with no effect on GLUT4. Glucose deprivation increased the total cellular GLUT1 protein in parallel with the transport activity, whereas GLUT4 was unaltered. The specific PI 3-kinase inhibitor wortmannin inhibited the effect of glucose deprivation on transport activity and also on GLUT1 synthesis. Glucose deprivation produced a moderate, biphasic increase in the activity of the protein kinase Akt/PKB that was inhibitable by wortmannin. When wortmannin was added after stimulation of cells in order to assess the internalization rate of transporters, the effect of insulin was reversed considerably faster (T1/2 = 18 min) than that of glucose deprivation (T1/2 > 60 min). These data are consistent with the conclusion that the effect of glucose deprivation reflects a specific, Akt-dependent de-novo synthesis of GLUT1, and not of GLUT4, and its insertion into a plasma membrane compartment which is distinct from that of the insulin-sensitive GLUT1.

An algorithm for evaluating human cytotoxic T lymphocyte responses to candidate AIDS vaccines.

Development of an effective vaccine against HIV-1 will likely require the induction of a broad array of immune responses, including virus-specific CTLs and neutralizing antibodies. One promising vaccine approach involves live recombinant canarypox (CP)-based vectors (ALVAC) containing multiple HIV-1 genes. In phase I clinical trials in HIV-1-seronegative volunteers, the cumulative rate of detection of HIV-1-specific CTLs has been as high as 60-70%. In the present study, the factors associated with CTL responsiveness were evaluated in a subset of vaccinees immunized with a CP vector expressing portions of the gag, pro, and env genes of HIV-1 (ALVAC-HIV). CTL responses were detected in one of seven examined. While the responding individual had both CD4+ and CD8+ CTLs directed at multiple HIV-1 antigens, this response was not detectable 1 year after the last vaccination. In-depth characterization of "CTL nonresponders" showed that nonresponsiveness was not associated with defects in antigen processing or presentation. A generalized defect in CTL responsiveness was ruled out by parallel assays to detect CMV-specific CTLs from these same volunteers. Furthermore, HIV-1-specific memory CTLs were not detectable by peptide stimulation or by a novel technique for flow cytometric visualization of Gag epitope-specific T lymphocytes while HIV-1-seropositive donors frequently had 0.1-3% of CD8+ cells stain positively for this epitope (SLYNTVATL). Taken together, these results suggest that the lack of detectable HIV-1 CTLs in these volunteers was not due to classic MHC-linked nonresponsiveness.

Meningococcal disease in urban south western Sydney, 1990-1994.

BACKGROUND: There has been a sustained increase in incidence of meningococcal disease throughout Australia since 1987. In south western Sydney the incidence is higher than the national rate and a cluster of cases occurred in 1991 resulting in a widespread vaccination programme. AIMS: To investigate the clinical demographics of patients with meningococcal disease treated in south western Sydney, and to differentiate meningococcal strains to understand better the epidemiology in this urban setting. In addition, to investigate whether delays in diagnosis of meningococcal disease and institution of appropriate treatment were occurring. METHODS: Retrospective classification of notified cases as meningitis, septicaemia, meningitis/septicaemia, and other syndromes. Clinical information recorded to establish patterns of disease, delays in diagnosis and appropriate treatment, and outcome. Microbiological classification of organisms isolated by serogroup, serotype and subtype. RESULTS: Meningococcal disease primarily affects young children in winter months in south western Sydney, with a secondary peak of incidence in the 15-20 year old age group. 20.7% presented with meningitis only, 22.4% with septicaemia only, and 53.4% with meningitis/septicaemia. There was a delay in diagnosis and institution of appropriate treatment of more than two hours in 21/58 (36.2%) patients including three of the six who died. No patient had received a parenteral antibiotic prior to coming to hospital -18.9% had received an oral antibiotic. The use of antibiotics before diagnostic lumbar puncture decreased the number of positive CSF cultures. However, in all but one patient with negative cultures there was other microbiological evidence of meningococcal disease. The mortality rate was highest (30.8%) in patients with septicaemia only, 6.5% in patients with meningitis/septicaemia and 0% in patients with meningitis only. Serogroup C was the predominant organism in all age groups. The predominant serotype was 2b (80% of serogroup C isolates). Subtypes were more variable but P1.2 occurred in 66.7% of serogroup C strains. CONCLUSIONS: There is a need for more education in our Health Area to improve the time taken to diagnose and institute appropriate treatment. The predominance of serogroup C is unusual in urban Australia where national data show serogroup B organisms predominate. Meningococci of phenotype C:2b:P1.2 have continued to cause disease in our Health Area for the past five years. This phenotype is uncommon in other areas of Australia.

Vasoproliferation in the neonatal dog model of oxygen-induced retinopathy.

PURPOSE: To examine the time course and relative degree of proliferative response associated with revascularization after hyperoxic insult in the dog model of oxygen-induced retinopathy. METHODS: Mitotic cell profiles (MCPs) were counted in serial cross-sections of ADPase flat-embedded retinas of air-reared control 8-, 15-, and 22-day-old dogs and of age-matched oxygen treated animals (4 days, 100% oxygen) after return to normoxia. Sectioning and analysis were performed along the radial axis of the forming primary vasculature from optic nerve head to periphery. RESULTS: In air-reared control animals, lumenal-associated cell mitosis was low, with an average of 9.6 MCPs/mm2 of nerve fiber layer tissue in the 8-day-old dogs, 6.5 MCPs/mm2 in the 15-day-old dogs, and 8.4 MCPs/mm2 in the 22-day-old dogs. In oxygen-treated animals, however, the number of lumenal-associated MCPs was significantly higher, with an average of 52.5 MCPs/mm2 of tissue in the 8-day-old dogs, 45.1 MCPs/mm2 in the 15-day-old dogs, and 26.8 MCPs/mm2 in the 22-day-old dogs. Additionally, extracellular spaces in avascular retina were obliterated in oxygen-treated animals. CONCLUSIONS: This study demonstrates that in the neonatal dog, revascularization after hyperoxic insult involves a period of marked vasoproliferation that peaks somewhere between 3 to 10 days after return to room air. Oxygen-induced changes in the extravascular milieu are likely to affect the pattern of reforming vasculature and may restrict growth anteriorly.

Immunohistochemical insights into sickle cell retinopathy.

Dynamic vaso-occlusive and vaso-proliferative events occur in sickle cell retinopathy. Using streptavidin peroxidase immunohistochemistry, we investigated changes in distribution and relative levels of components in the fibrinolytic system and growth factors in retina and choroid from 2 sickle cell patients: a 20 month old SS patient and a 54 year old SC patient. Antigen localization in the sickle cell patients was compared to localization from 2 non-sickle cell, non-diabetic control subjects. In the fibrinolytic system, tissue plasminogen activator (tPA) localization and immunoreactivity were comparable in all eyes, but plasminogen activator inhibitor-1 (PAI-1) immunoreactivity was elevated within the walls of retinal vessels in the sickle cell tissue. Immunoreactive fibrin was often observed within the lumen of retinal and choroidal vessels and in choroidal neo-vascularization (CNV) in sickle cell subjects. Blood vessels containing fibrin generally exhibited elevated PAI-1 immunoreactivity. Von Willebrand's factor (vWf) and basic fibroblast growth factor (bFGF) immunoreactivity in sickle cell patients were elevated in choriocapillaris and the walls of some retinal vessels. Transforming growth factor-beta 1 (TGF-beta 1) immunoreactivity was significantly lower in sickle cell choriocapillaris than in controls. In chorioretinal pigmented lesions of the SC patient, bFGF and TGF-beta 1, beta 2, and beta 3 immunoreactivity was present within migrating retinal pigment epithelial (RPE) cells. Our interpretation of the data presented in this case study is that fibrin deposition within retinal and choroidal vessels of sickle cell subjects may occur due to elevated PAI-1 activity. Moreover, vaso-occlusions of choroidal vessels may influence the expression of growth factors in choriocapillaris endothelium, which could stimulate formation of choroidal neovascularization. Finally, fibrosis and gliosis in and near chorioretinal pigmented lesions may be stimulated by RPE production of bFGF and TGF-beta's.

Age and skill differences in adaptive competence.

Previous research has documented qualitative changes in certain cognitive abilities during the older adult years, such as in short-term memory, perceptual and motor skills, and attentional capacities. Other work has suggested that a number of significant age-related changes, across a variety of cognitive abilities, are based on social experiences, such as occupational or recreational activities. The current study is based on earlier research by Perlmutter and her colleagues (1990) and examines age and skill-related differences among adults engaged in a social-recreational activity. BINGO players, ranging in age from nineteen to seventy-four, and having from less than two months to over twenty years of playing experience, were given a variety of psychometric, cognitive, and experimental measures. The participants were also observed as they played real BINGO games. No age-related differences were found on the psychometric or memory measures, suggesting that BINGO playing experience may have positive benefits for many older adults. Skilled players at all age levels were found to be more efficient in their game-playing actions. The oldest and most experienced players did not differ from the younger, equally experienced, players on the cognitive and skill-based tasks. These findings demonstrate the need to investigate adaptive competence in those situations in which social-environmental factors play a role in enhancing older adults' cognitive skills.

Launching a national helpline.

Launched in October 1990, the National Asthma Campaign telephone helpline answered over 10,000 enquiries in its first 18 months of operation. Most callers were either parents of children with asthma or those with the condition themselves. STEVE CRONE et al describe the operation of the 'Asthma helpline' and the lessons learned about clients' concerns and information needs.

Heterogeneity in localization of isoforms of TGF-beta in human retina, vitreous, and choroid.

PURPOSE: The purpose of this work was to investigate further the immunohistochemical localization of transforming growth factor (TGF)-beta 1 to photoreceptors, which we had previously observed, to elucidate the cell types of origin for TGF-beta 1, and to determine sites of localization for TGF-beta 2 and beta 3 in the posterior segment of the human eye. METHOD: Streptavidin-peroxidase immunohistochemistry was used to localize TGF-beta antibodies in sections from cryopreserved human posterior segments from six adult donors. Two recently described polyclonal antibodies to TGF-beta 1 (anti-CC[1-30] and anti-LC[1-30]) and antibodies against TGF-beta 2 and beta 3 were employed in this study. Other studies suggest that anti-LC(1-30) antibody recognizes pre-pro-TGF-beta 1 and therefore sites of production, while anti-CC(1-30) recognizes secreted forms of TGF-beta 1. RESULTS: Regional labeling of choriocapillaris was observed in all eyes using anti-LC(1-30) (anti-pre-pro-beta 1). Anti-CC(1-30) (anti-secr-beta 1) was localized predominantly in photoreceptor inner and outer segments in all eyes. Outer segment localization appeared identical to anti-opsin localization, indicating that this form of TGF-beta 1 is most likely intracellular. TGF-beta 2 was observed predominantly in the connective tissue of long ciliary arteries in choroid and in photoreceptor outer segments in all eyes. TGF-beta 3 was observed in isolated individual cells in choroid and retina. Vitreous hyalocytes were the only cell type examined that were immunoreactive for all four forms of TGF-beta studied. CONCLUSION: The heterogeneity in localization of TGF-beta s in the human posterior eye suggests that TGF-beta s are produced, used, and degraded locally. TGF-beta 1 produced by the choriocapillaris may be stored or used by photoreceptors.

Comparison of the Semmes-Weinstein monofilaments with the Pressure-Specifying Sensory Device.

Measuring human sensibility remains a challenge, with the primary limitation being the instrumentation traditionally available. The Pressure-Specifying Sensory Device (PSD) permits quantitation of the human pressure perception threshold by means of transducers that couple two rounded prongs to a personal computer. If just one prong is perceived in constant contact with the skin, the cutaneous pressure threshold is directly obtained, scaling along a continuum from .05 to 100 g/mm2 (readout on computer monitor). This measurement is analogous to that obtained with the series of Semmes-Weinstein monofilaments (SWM) (readout in logarithmic marking on nylon rod). The present study evaluated twenty normal volunteers and ten nerve-impaired patients with both the PSD and the SWM. There was a poor correlation between the measurement offeree (r = 0.21) and pressure (r = 0.29) obtained with the PSD and the SWM. This study reaffirms the value of measuring pressure perception threshold during the sensibility evaluation, while calling attention to selection of instrumentation for obtaining this measurement.