Magnetic monopole density and antiferromagnetic domain control in spin-ice iridates.

Magnetically frustrated systems provide fertile ground for complex behaviour, including unconventional ground states with emergent symmetries, topological properties, and exotic excitations. A canonical example is the emergence of magnetic-charge-carrying quasiparticles in spin-ice compounds. Despite extensive work, a reliable experimental indicator of the density of these magnetic monopoles is yet to be found. Using measurements on single crystals of Ho2Ir2O7 combined with dipolar Monte Carlo simulations, we show that the isothermal magnetoresistance is highly sensitive to the monopole density. Moreover, we uncover an unexpected and strong coupling between the monopoles on the holmium sublattice and the antiferromagnetically ordered iridium ions. These results pave the way towards a quantitative experimental measure of monopole density and demonstrate the ability to control antiferromagnetic domain walls using a uniform external magnetic field, a key goal in the design of next-generation spintronic devices.

Superconductivity and the upper critical field in the chiral noncentrosymmetric superconductor NbRh2B2.

NbRh2B2 crystallises in a chiral noncentrosymmetric structure and exhibits bulk type-II superconductivity below [Formula: see text] K. Here we show that the temperature dependence of the upper critical field deviates from the behaviour expected for both Werthamer-Helfand-Hohenberg and the Ginzburg-Landau models and that [Formula: see text] T exceeds the Pauli paramagnetic limit, [Formula: see text] T. We explore the reasons for this enhancement. Transverse-field muon spectroscopy measurements suggest that the superconducting gap is either s-wave or [Formula: see text]-wave, and the pressure dependence of [Formula: see text] reveals the superconducting gap is primarily s-wave in character. The magnetic penetration depth [Formula: see text] nm. Heat capacity measurements reveal the presence of a multigap [Formula: see text]-wave superconducting order parameter and moderate electron-phonon coupling.

Unexpected Relations of Historical Anthrax Strain.

In 1998, it was claimed that an 80-year-old glass tube intentionally filled with Bacillus anthracis and embedded in a sugar lump as a WWI biological weapon still contained viable spores. Today, genome sequencing of three colonies isolated in 1998 and subjected to phylogenetic analysis surprisingly identified a well-known B. anthracis reference strain isolated in the United States in 1981, pointing to accidental laboratory contamination.IMPORTANCE Next-generation sequencing and subsequent phylogenetic analyses are useful and reliable tools for the classification of recent and historical samples. The reliability of sequences obtained and bioinformatic algorithms has increased in recent years, and research has uncovered the identity of a presumed bioweapon agent as a contaminant.

Presymptomatic prediction of sepsis in intensive care unit patients.

Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1beta (IL-1beta), IL-6, IL-8, and IL-10, tumor necrosis factor-alpha, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers.

Accumulation of embedded solitons in systems with quadratic nonlinearity.

Previous numerical studies have revealed the existence of embedded solitons (ESs) in a class of multiwave systems with quadratic nonlinearity, families of which seem to emerge from a critical point in the parameter space, where the zero solution has a fourfold zero eigenvalue. In this paper, the existence of such solutions is studied in a three-wave model. An appropriate rescaling casts the system in a normal form, which is universal for models supporting ESs through quadratic nonlinearities. The normal-form system contains a single irreducible parameter epsilon, and is tantamount to the basic model of type-I second-harmonic generation. An analytical approximation of Wentzel-Kramers-Brillouin type yields an asymptotic formula for the distribution of discrete values of epsilon at which the ESs exist. Comparison with numerical results shows that the asymptotic formula yields an exact value of the scaling index, -65, and a fairly good approximation for the numerical factor in front of the scaling term.

Macromolecular organisation of recombinant Yersinia pestis F1 antigen and the effect of structure on immunogenicity.

Yersinia pestis, the causative organism of plague, produces a capsular protein (fraction 1 or F1 antigen) that is one of the major virulence factors of the bacterium. We report here the production, structural and immunological characterisation of a recombinant F1 antigen (rF1). The rF1 was purified by ammonium sulfate fractionation followed by FPLC Superose gel filtration chromatography. Using FPLC gel filtration chromatography and capillary electrophoresis, we have demonstrated that rF1 antigen exists as a multimer of high molecular mass. This multimer dissociates after heating in the presence of SDS and reassociation occurs upon the removal of SDS. Using circular dichroism, we have monitored the reassociation of monomeric rF1 into a multimeric form. Mice immunised with monomeric or multimeric rF1 develop similar immune responses, but mice immunised with monomeric rF1 were significantly less well protected against a challenge of 1 x 10(6) cfu of Y. pestis than mice immunised with multimeric rF1 (1/7 compared with 5/7). The significance of this result in terms of the structure and the function of rF1 is discussed.

Encouraging consensus cost effective drug therapy: five years experience with a hospital drug utilisation review programme.

AIMS: To evaluate the impact of a local hospital drug utilisation review (DUR) programme over the first 5 years of operation. METHODS: The local drug utilisation review programme focussed on improving the quality and cost effectiveness of drug use. It began with the introduction of a preferred medicines list (PML) to the six Christchurch hospitals in December 1990. The drug utilisation review program was evaluated by monitoring local and national hospital drug costs and local patient numbers. Compliance with the preferred medicines list was measured and clinical users were surveyed to gauge their response to the programme. The effects of guidelines were also evaluated in selected drug therapy areas. RESULTS: Local annual hospital drug costs increased 20% from $8.26M in 1991 to $9.96M in 1995. During this time patient numbers increased by 16% and national hospital drug sales have increased 65%. Before the programme introduction local drug costs were increasing on average 46% per year. Compliance with the preferred medicines list was 98%. Of the clinical users surveyed, 88% of respondents felt the programme caused no major restriction of personal clinical practice. Guidelines on ondansetron ceftriaxone and asthma drug therapy helped improve the quality of drug therapy. CONCLUSION: The local drug utilisation review programme, helped facilitate improved quality drug therapy and contain overall hospital drug costs.

Psychological and sexual aspects of the menopause and HRT.

Despite the clinical impressions that there are considerable psychological benefits from HRT, there is only clear evidence for amelioration of psychological symptoms (including improvement in cognitive function) in women who have undergone a surgical menopause. Otherwise in the natural menopause it remains unclear which, if any, non-sexual psychological symptoms respond directly to oestrogen except as a secondary response to reduction in physical symptoms. Overall, it has to be said that there is little scientific backing for hormonal treatment of psychological problems on their own around the time of the natural menopause. In most cases psychological treatment or counselling will be more appropriate than HRT. It must be remembered that the prevalence of psychological symptoms in the menopause and gynaecology clinic is high just as it is in all hospital settings. The task is to identify which women: 1. Have a predominance of psychological symptoms and might have psychiatric disorders. They may have presented in the clinic because they also happen to be menopausal, but it may well be that the psychiatric disorder has a quite independent aetiology. They will benefit from specific treatment for that disorder. 2. Have, and complain of, low moods or other non-specific psychological symptoms and have presented in the clinic because they are menopausal. They might benefit from practical, supportive help with current and ongoing stresses and strains. 3. Present appropriate menopausal complaints and only on enquiry reveal their psychological problems. In particular, disorders such as depressive illness, anxiety states and alcohol abuse can present with physical symptoms including ones which mimic vasomotor ones. This group may well be non-responders to HRT. Women requiring particular consideration might be those with other health problems (particularly chronic ones that might carry on in to old age) who are possibly more at risk of developing depression as they pass through the menopause. There is clearer evidence that HRT has beneficial effects on sexual function. When sexual symptoms are presented it is worth clarifying the exact features contributing to the complaint. Is it a problem of sexual interest, of infrequency of sexual activity, of vaginal dryness and dyspareunia, or is it a mixture of these complaints? Reduction of sexual interest and reduced sexual activity with the partner and possibly orgasm may accompany the menopause. Oestrogens have been shown to have some beneficial effect on sexual desire. Where oestrogen alone is ineffective, testosterone is usually beneficial. This treatment effect is particularly clear in surgically menopausal women. Non-menopausal aspects of the sexual relationship must be considered too. These aspects include the quality of the relationship, the sexual performance of the partner (since sexual desire decreases in both sexes with age), and age-related changes in self-image. These issues may need to be addressed at a simple health education level or with specific counselling. Although a woman's motivation or desire might change as a result of HRT, on its own this will not influence the frequency of intercourse or response during intercourse unless the partner variables permit this. The situation is more straightforward when problems of postmenopausal vaginal dryness and dyspareunia are the key issues. Oestrogens have been shown to be highly effective in such circumstances. It is also worth noting that regular and continued sexual activity has been found to protect against vaginal dryness.

Asthma management at Christchurch Hospital: compliance with guidelines.

AIM: To audit compliance with guidelines for the assessment and management of adult patients admitted to Christchurch Hospital with acute asthma. METHODS: An asthma admission form and management guidelines, based on international consensus statements, were designed for use by resident staff at Christchurch Hospital. Compliance with these guidelines was audited during the winter of 1994 by means of retrospective case record review. RESULTS: One hundred and forty three admissions were screened. The form was used in 99 patients (69%), of which 97 had records available for audit. Sixty two patients were admitted under general medical services and 35 under respiratory specialist services. The median age was 34 years (range 14-84) and 77% were female. The history including interval status was adequately documented in over 95% of cases. Peak flow rate was recorded on admission in 93 patients (96%) and spirometry in 62 (64%). During the acute phase of treatment 528 items were prescribed, of which 382 (72%) were appropriate according to the guidelines. The major area (55%) of nonguideline prescribing was the use of nebulised ipratropium in addition to salbutamol for mild or moderate asthma. Written evidence of asthma education was present in 42 (43%). In 34 patients (35%) there was specific reference to the introduction of an asthma action plan. Of the 33 smokers only 17 appeared to have been given smoking cessation advice. Discharge prescribing complied with the guidelines in 71%. The most common variation from the guidelines for discharge therapy related to the manner of prednisone dose reduction. The readmission rate at 1 month was 11%. CONCLUSIONS: The introduction of an asthma admission form enhanced the quality of clinical data gathering by junior staff. Compliance with management guidelines was adequate. Specific sections pertaining to the use of chest radiographs, arterial blood gases and the prescribing of ipratropium and prednisone will be reviewed in updated guidelines.

Compliance with guidelines results in appropriate ondansetron prescribing at Christchurch Hospital.

AIM: To assess compliance with established consensus derived guidelines for ondansetron therapy and to estimate the cost of any non-guideline use. METHODS: All inpatients (including paediatric patients) at Christchurch Hospital who received ondansetron during August 1993 were identified by daily review of medication charts. Outpatients who received ondansetron prescriptions were identified from pharmacy records. All patients' medical records were then examined and ondansetron therapy was compared with the guideline recommendations for indication and dosage. The total cost of ondansetron for each patient was also calculated. RESULTS: Ondansetron was prescribed for 64 patients (41 female, 23 male) during the one month period. Fifty patients received ondansetron therapy in accordance with all indication and dosage aspects of the guidelines. The main guideline indication for use was highly emetogenic chemotherapy with 28 patients. Fifteen patients received ondansetron because of failure of standard antiemetic therapy and nine because they were paediatric chemotherapy patients. Of the 12 patients who received ondansetron outside the guidelines indications, nine had received 'moderately highly' emetogenic chemotherapy (whereas the guidelines state 'highly' only), two had severe asthma, one received radiotherapy. Two patients did not comply with the dosage recommendations as they received ondansetron more than 24 hours after the initial cytotoxic dose. Total ondansetron expenditure for the period was $12,789 (inpatient $8492 outpatient $4297). Expenditure related to the nonguideline usage was $536 (4.2% of the total monthly ondansetron expenditure). CONCLUSION: There was high compliance with the guidelines. This supports the use of guidelines in encouraging appropriate prescribing.

Shear stress activates cytosolic phospholipase A2 (cPLA2) and MAP kinase in human endothelial cells.

Intracellular signalling events that govern endothelial responses to shear are incompletely defined. In this study confluent human endothelial cells were subjected to shear. At shear levels of 1.04, 2.92, 5.31 and 8.3 dynes/cm2, which are in the range of those that occur in vessels in venous and arterial circulations, the activity of cPLA2 was increased above control levels. To examine pathways by which cPLA2 may be activated in response to shear, we assayed the p42 isoform of MAP kinase (ERK-2) and found increased activity in cells exposed to shear. Our findings demonstrate for the first time that cPLA2 and MAP kinase p42 are activated by shear in human endothelial cells, and add to evidence from other systems that indicates that the two enzymes have related signalling functions.

Optimising the removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.

1. The efficacy of ZnDTPA administered in drinking water has been investigated for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates. 2. The continual administration of ZnDTPA 95 mumol kg-1 d-1 over a 21 d interval commencing 1 h after exposure reduced the 238Pu content of the lungs and total body to 2% and 8% of those in untreated animals; the corresponding values for 241Am were 3% and 5%. 3. The continual intakes of 950 mumol kg-1 d-1, intermittent intakes of 3600 mumol kg-1 d-1 and the repeated injection of 30 mumol kg-1 body weight were considered no more effective. 4. All orally administered concentrations of ZnDTPA, commencing 7 d after exposure, reduced the total body contents of 238Pu and 241Am to 17% and 20% of controls by 28 d. 5. Histopathological examination of the kidneys, liver and gastrointestinal tract showed no apparent effects of these treatment protocols. 6. It is concluded that the oral administration of ZnDTPA could be an effective treatment for the removal of inhaled transportable forms of Pu and Am after human exposure.

Clinical and economic considerations in the use of third-generation oral cephalosporins.

A number of oral third-generation cephalosporins (cefixime, cefetamet pivoxil, ceftibuten and cefpodoxime proxetil) have been widely trialled and are becoming available. In addition, cefdinir may also be marketed. Compared with first- and second-generation agents, the oral third-generation cephalosporins have an improved antibacterial spectrum and reduced minimum inhibitory concentrations against common Gram-negative pathogens. In contrast, with the exception of cefdinir, they are less active against Staphylococcus aureus. They have favourable pharmacokinetic profiles and are generally administered in once- or twice-daily regimens. They are well tolerated, but cefixime has been associated with a particularly high rate of diarrhoea. Possible clinical indications for the use of oral third-generation cephalosporins include upper and lower respiratory, genitourinary and soft-tissue infections and follow-on treatment of severe infections requiring hospitalisation. At present, these drugs offer no particular clinical advantages over standard therapy in most circumstances. However, they may be considered where there is hypersensitivity to penicillins, a high incidence of resistance to first-line therapy in the community, or failure of standard therapy. Further studies are needed to define the efficacy of oral third-generation agents in the prevention of rheumatic fever and as follow-on therapy for severe infections. The oral third-generation cephalosporins are generally more expensive than standard agents, but detailed studies that include extended costs (e.g. treatment of adverse effects, treatment of clinical failure, return visits to physicians) have yet to be reported.

Decorporation of thorium-228 from the rat by 3,4,3-LIHOPO and DTPA after simulated wound contamination.

1. With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treatment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2. In all cases 3,4,3-LIHOPO was appreciably more effective than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3. Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body content of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The corresponding values using repeated DTPA administration were 80% and 54%. 4. It is concluded that 3,4,3-LIHOPO represents, potentially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contaminated by 228Th.

Hospital drug therapy cost containment through a preferred medicines list and drug utilisation review system.

AIM: To measure the economic impact of the introduction of a preferred medicines list and drug utilisation review process on drug therapy costs at the six Christchurch hospitals in the Canterbury Area Health Board. METHODS: The preferred medicines list, a consensus derived recommended drug list, was introduced along with a drug utilisation review process in December 1990. Detailed drug therapy costs were collected from the pharmacy computer for the 1990/1 and 1991/2 hospital financial years. Data was analysed under the 15 British National Formulary drug groups and also 14 other categories. National hospital drug costs based on sales to hospitals and local drug cost trends prior to the preferred medicine list system introduction were used as baseline measures. Hospital patient discharge numbers and patient days were also recorded. RESULTS: Prior to the preferred medicines list introduction local drug therapy costs had been rising on average 30% per year. Between 1990/1 and 1991/2 total drug costs fell by 2% from $12.16M to $11.86M while nationally, drug sales to hospitals increased by 15%. Included in the local expenditure were drugs external to the preferred medicine list/drug utilisation review system whose costs are reimbursed to the area health board. When these costs were deducted, inpatient drug costs fell by 11% from $8.76M to $7.7M. In the 29 categories reviewed, 17 had decreases, while the remaining areas increased. Total patient numbers during the period increased by 3% while total patient days decreased by 10%. CONCLUSION: The preferred medicines list and the associated drug utilisation review process played a major role in the reduction of inpatient drug therapy costs at the Christchurch hospitals. Other factors such as cost shifting or changes in community drug use may have also been responsible for some of the savings.

Comparative efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat after simulated wound contamination as nitrates.

With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 238Pu and 241Am from the rat after subcutaneous (s.c.) and intramuscular (i.m.) injection of about 200 Bq of each actinide (0.3 ng Pu, 1.6 ng Am). After the s.c. deposition of 238Pu and 241Am, both ligands were more effective after local administration than (in decreasing order) their repeated interperitoneal (i.p.) injection, single i.p. injection and continuous infusion. Dosages of 3 mumol kg-1 of 3,4,3-LIHOPO were at least as effective as 30 mumol kg-1 DTPA after each mode of administration. The most effective regimen of those investigated for s.c. 238Pu and 241Am involved local administration of 30 mumol kg-1 of 3,4,3-LIHOPO at 30 min followed by i.p. injections at 6 h, 1, 2 and 3 day. By day 7 after exposure, the amounts of 238Pu and 241Am retained in the body were 2 and 7% of those in controls, respectively and 10 and four times less than when DTPA was administered using the same regimen. The ligand 3,4,3-LIHOPO was more effective for 238Pu and 241Am after their i.m. injection. This was attributed to the greater retention of these actinides at the wound site (97 versus 67%) when treatment commenced. After a single local injection of 30 mumol kg-1 at 30 min, the amounts of 238Pu and 241Am retained in the body at 7 day were 0.9 and 0.8% of controls. These values were 34 and 27 times less than after local and repeated i.p. injections of DTPA at dosages of 30 mumol kg-1. It is concluded that the administration of 3,4,3-LIHOPO represents potentially a most significant advance in the treatment of wound contamination by 238Pu and 241Am by chelating agents.

Rapid analysis of PCR components and products by acidic non-gel capillary electrophoresis.

A capillary electrophoresis system has been developed which has the ability to rapidly analyse DNA restriction fragments, PCR products, oligonucleotides and complex deoxyribonucleoside tri-, di- and mono-phosphate mixtures in a single separating medium. Separations are performed in an internally coated capillary containing a solution of linear polymers. The separation of all DNA species is achieved through the novel use of acidic rather than alkaline pH. This has the added advantage of preserving the internal capillary coating. The use of the technique is described for rapid, high resolution separation of pBR322 and phi X174 DNA restriction digests, quality control of dNTP and oligonucleotide primer PCR components, detection of a PCR amplified region of lambda-phage DNA and detection of a PCR amplified human hypervariable region of forensic interest. The technique is termed "acidic non-gel capillary electrophoresis".

Radiological implications of inhaled 239Pu and 241Am in dusts at the former nuclear test site in Maralinga.

The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract.