Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent Fever?

Background: Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever.Methods: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%).Results: At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak >500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively.Conclusion: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses

Utility of beta-glucan for the diagnosis of invasive fungal infections

(1,3)-b-D-glucan is a component of the fungal cell wall. New assays have made it possible to detect this molecule in a variety of clinical samples such as blood, cerebrospinal fluid, and bronchioalveolar lavage fluid. Detection of this molecule through several assays has been validated as an adjunct method to diagnose invasive fungal infections. With several decades of data and recent positive meta-analyses, these assays have now been sufficiently studied and are ready to enter the mainstream of diagnosis in medical mycology.

Examining chemical compound biodegradation at low concentrations through bacterial cell proliferation.

We show proof of principle for assessing compound biodegradation at 1-2 mg C per L by measuring microbial community growth over time with direct cell counting by flow cytometry. The concept is based on the assumption that the microbial community will increase in cell number through incorporation of carbon from the added test compound into new cells in the absence of (as much as possible) other assimilable carbon. We show on pure cultures of the bacterium Pseudomonas azelaica that specific population growth can be measured with as low as 0.1 mg 2-hydroxybiphenyl per L, whereas in mixed community 1 mg 2-hydroxybiphenyl per L still supported growth. Growth was also detected with a set of fragrance compounds dosed at 1-2 mg C per L into diluted activated sludge and freshwater lake communities at starting densities of 10(4) cells per ml. Yield approximations from the observed community growth was to some extent in agreement with standard OECD biodegradation test results for all, except one of the examined compounds.

Utility scores associated with the world health organisation drinking risk-level classification in alcohol dependence

BACKGROUND: Extensive research exists estimating the effect hazardous alcohol¦use on morbidity and mortality, but little research quantifies the association between¦alcohol consumption and utility scores in patients with alcohol dependence.¦In the context of comparative research, the World Health Organisation (WHO)¦proposed to categorise the risk for alcohol-related acute and chronic harm according¦to patients' average daily alcohol consumption. OBJECTIVES: To estimate utility¦scores associated with each category of the WHO drinking risk-level classification¦in patients with alcohol dependence (AD). METHODS: We used data from¦CONTROL, an observational cohort study including 143 AD patients from the Alcohol¦Treatment Center at Lausanne University Hospital, followed for 12 months.¦Average daily alcohol consumption was assessed monthly using the Timeline Follow-¦back method and patients were categorised according to the WHO drinking¦risk-level classification: abstinent, low, medium, high and very high. Other measures¦as sociodemographic characteristics and utility scores derived from the EuroQoL¦5-Dimensions questionnaire (EQ-5D) were collected every three months.¦Mixed models for repeated measures were used to estimate mean utility scores¦associated with WHO drinking risk-level categories. RESULTS: A total of 143 patients¦were included and the 12-month follow-up permitting the assessment of¦1318 person-months. At baseline the mean age of the patients was 44.6 (SD 11.8)¦and the majority of patients was male (63.6%). Using repeated measures analysis,¦utility scores decreased with increasing drinking levels, ranging from 0.80 in abstinent¦patients to 0.62 in patients with very high risk drinking level (p_0.0001).¦CONCLUSIONS: In this sample of patients with alcohol dependence undergoing¦specialized care, utility scores estimated from the EQ-5D appeared to substantially¦and consistently vary according to patients' WHO drinking level.

First-generation linkage map for the European tree frog (Hyla arborea) with utility in congeneric species.

BACKGROUND: Western Palearctic tree frogs (Hyla arborea group) represent a strong potential for evolutionary and conservation genetic research, so far underexploited due to limited molecular resources. New microsatellite markers have recently been developed for Hyla arborea, with high cross-species utility across the entire circum-Mediterranean radiation. Here we conduct sibship analyses to map available markers for use in future population genetic applications. FINDINGS: We characterized eight linkage groups, including one sex-linked, all showing drastically reduced recombination in males compared to females, as previously documented in this species. Mapping of the new 15 markers to the ~200 My diverged Xenopus tropicalis genome suggests a generally conserved synteny with only one confirmed major chromosome rearrangement. CONCLUSIONS: The new microsatellites are representative of several chromosomes of H. arborea that are likely to be conserved across closely-related species. Our linkage map provides an important resource for genetic research in European Hylids, notably for studies of speciation, genome evolution and conservation.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

BACKGROUND: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. METHODS: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. RESULTS: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. CONCLUSIONS: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.

Using flow cytometry for in situ monitoring of antimicrobial compound production in the biocontrol bacterium Pseudomonas fluorescens CHA0

Pseudomonas fluorescens strain CHA0 is able to protect plants against a variety of pathogens, notably by producing the two antimicrobial compounds 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin (PLT). The regulation of the expression of these compounds is affected by many biotic factors, such as fungal pathogens, rhizosphere bacteria as well as plant species. Therefore, the influence of some plant phenolic compounds on the expression of DAPG and PLT biosynthetic genes has been tested using GFP-based reporter, monitored by standard fluometry and flow cytometry. In situ experiments were also performed with cucumber plants. We found that several plant metabolites such as IAA and umbelliferone are able to modify significantly the expression of DAPG and PLT. The use of flow cytometry with autofluorescents proteins seems to be a promising method to study rhizobacteria-plant interactions.

A CT-based study investigating the relationship between pedicle screw placement and stimulation threshold of compound muscle action potentials measured by intraoperative neurophysiological monitoring.

PURPOSE: Neurophysiological monitoring aims to improve the safety of pedicle screw placement, but few quantitative studies assess specificity and sensitivity. In this study, screw placement within the pedicle is measured (post-op CT scan, horizontal and vertical distance from the screw edge to the surface of the pedicle) and correlated with intraoperative neurophysiological stimulation thresholds. METHODS: A single surgeon placed 68 thoracic and 136 lumbar screws in 30 consecutive patients during instrumented fusion under EMG control. The female to male ratio was 1.6 and the average age was 61.3 years (SD 17.7). Radiological measurements, blinded to stimulation threshold, were done on reformatted CT reconstructions using OsiriX software. A standard deviation of the screw position of 2.8 mm was determined from pilot measurements, and a 1 mm of screw-pedicle edge distance was considered as a difference of interest (standardised difference of 0.35) leading to a power of the study of 75 % (significance level 0.05). RESULTS: Correct placement and stimulation thresholds above 10 mA were found in 71 % of screws. Twenty-two percent of screws caused cortical breach, 80 % of these had stimulation thresholds above 10 mA (sensitivity 20 %, specificity 90 %). True prediction of correct position of the screw was more frequent for lumbar than for thoracic screws. CONCLUSION: A screw stimulation threshold of >10 mA does not indicate correct pedicle screw placement. A hypothesised gradual decrease of screw stimulation thresholds was not observed as screw placement approaches the nerve root. Aside from a robust threshold of 2 mA indicating direct contact with nervous tissue, a secondary threshold appears to depend on patients' pathology and surgical conditions.

Biomarqueurs associés à la dyspnée et douleurs thoraciques: quelle utilité clinique [Biomarkers associated with dyspnea and chest pain: which cinical utility?].

Dyspnea and chest pain are typical reasons for consultations. biomarkers (CRP, procalcitonin, NT-proBNP, troponins, D-dimers) can have an interest for the diagnosis, the prognosis and the follow-up of several pathologies. There are however numerous pitfalls and limitations between the discovery of a biomarker and the utility in clinical practice. It is essential to always estimate a pre-test probability based on an attentive history and a careful physical examination, to know the intrinsic and extrinsic qualities of a test, and to determine a threshold of care. A biomarker should be used only if it modifies the patient's care and if it brings him a benefit compared to the patient who has no biomarker.

Audit report on the Regional Utility Service Systems Commission for the year ended June 30, 2011

Audit report on the Regional Utility Service Systems Commission for the year ended June 30, 2011

Theoretical approach to the magnetostructural correlations in spin-Peierls compound CuGeO3

A theoretical density-functional study has been carried out to analyze the exchange coupling in the chains of CuGeO3 using discrete models. The results show a good agreement with the experimental exchange coupling constant (J) together with a strong dependence of J with the Cu-O-Cu angle. The calculation of the J values for a distorted model indicates a larger degree of dimerization than those reported previously.