Fibre Bragg Gratings in Embedded Microstructured Optical Fibres Allow Distinguishing between Symmetric and Anti-Symmetric Lamb Waves in Carbon Fibre Reinforced Composites.

Conventional contact sensors used for Lamb wave-based ultrasonic inspection, such as piezo-electric transducers, measure omnidirectional strain and do not allow distinguishing between fundamental symmetric and anti-symmetric modes. In this paper, we show that the use of a single fibre Bragg grating created in a dedicated microstructured optical fibre allows one to directly make the distinction between these fundamental Lamb wave modes. This feature stems from the different sensitivities of the microstructured fibre to axial and transverse strain. We fabricated carbon fibre-reinforced polymer panels equipped with embedded microstructured optical fibre sensors and experimentally demonstrated the strain waves associated with the propagating Lamb waves in both the axial and transverse directions of the optical fibre.

Vibration Monitoring Using Fiber Optic Sensors in a Lead-Bismuth Eutectic Cooled Nuclear Fuel Assembly.

Excessive fuel assembly vibrations in nuclear reactor cores should be avoided in order not to compromise the lifetime of the assembly and in order to prevent the occurrence of safety hazards. This issue is particularly relevant to new reactor designs that use liquid metal coolants, such as, for example, a molten lead-bismuth eutectic. The flow of molten heavy metal around and through the fuel assembly may cause the latter to vibrate and hence suffer degradation as a result of, for example, fretting wear or mechanical fatigue. In this paper, we demonstrate the use of optical fiber sensors to measure the fuel assembly vibration in a lead-bismuth eutectic cooled installation which can be used as input to assess vibration-related safety hazards. We show that the vibration characteristics of the fuel pins in the fuel assembly can be experimentally determined with minimal intrusiveness and with high precision owing to the small dimensions and properties of the sensors. In particular, we were able to record local strain level differences of about 0.2 µÏµ allowing us to reliably estimate the vibration amplitudes and modal parameters of the fuel assembly based on optical fiber sensor readings during different stages of the operation of the facility, including the onset of the coolant circulation and steady-state operation.

Influence of fiber Bragg grating spectrum degradation on the performance of sensor interrogation algorithms.

The working principle of fiber Bragg grating (FBG) sensors is mostly based on the tracking of the Bragg wavelength shift. To accomplish this task, different algorithms have been proposed, from conventional maximum and centroid detection algorithms to more recently-developed correlation-based techniques. Several studies regarding the performance of these algorithms have been conducted, but they did not take into account spectral distortions, which appear in many practical applications. This paper addresses this issue and analyzes the performance of four different wavelength tracking algorithms (maximum detection, centroid detection, cross-correlation and fast phase-correlation) when applied to distorted FBG spectra used for measuring dynamic loads. Both simulations and experiments are used for the analyses. The dynamic behavior of distorted FBG spectra is simulated using the transfer-matrix approach, and the amount of distortion of the spectra is quantified using dedicated distortion indices. The algorithms are compared in terms of achievable precision and accuracy. To corroborate the simulation results, experiments were conducted using three FBG sensors glued on a steel plate and subjected to a combination of transverse force and vibration loads. The analysis of the results showed that the fast phase-correlation algorithm guarantees the best combination of versatility, precision and accuracy.

Managing invasive fungal infections: relying on clinical instincts or on a rational navigation system?

The management of invasive fungal disease in the immunocompromised host is complex and requires the specialized knowledge of physicians whose primary interest is actually the underlying disease rather than infectious complications. This Supplement aims to provide these physicians with some tools that may help to guide them through the maze of suspicion that an invasive fungal disease is present by offering an integrated care pathway of rational patient management. Such pathways will inevitably vary in detail in different centres and depend for their success on the presence of multidisciplinary teams and an explicit agreement on at least the minimum requirements for effective management. The integrated care pathways presented constitute an objective instrument to allow regular audits for recognizing opportunities to change practice if and when weaknesses are identified.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Erythrocyte vesiculation: a self-protective mechanism?

Previous studies demonstrated that 20% of haemoglobin is lost from circulating erythrocytes during their total lifespan by vesiculation. To study whether removal molecules other than membrane-bound haemoglobin were present in erythrocyte-derived vesicles, flow cytometry and immunoblot analysis were employed to examine the presence of phosphatidylserine (PS) and IgG, and senescent cell antigens respectively. It was demonstrated that 67% of glycophorin A-positive vesicles exposed PS, and that half of these vesicles also contained IgG. Immunoblot analysis revealed the presence of a breakdown product of band 3 that reacted with antibodies directed against senescent erythrocyte antigen-associated band 3 sequences. In contrast, only the oldest erythrocytes contained senescent cell antigens and IgG, and only 0.1% of erythrocytes, of all ages, exposed PS. It was concluded that vesiculation constitutes a mechanism for the removal of erythrocyte membrane patches containing removal molecules, thereby postponing the untimely elimination of otherwise healthy erythrocytes. Consequently, these same removal molecules mediate the rapid removal of erythrocyte-derived vesicles from the circulation.

Present situation in the treatment of invasive fungal infection.

Recent advances have made it possible to treat successfully conditions that for many years were considered incurable. In many cases, aggressive therapeutic or diagnostic techniques have been used. One resulting adverse event is a severely diminished immune response that, given the patient's situation, demands accurate and rapid treatment. Invasive fungal infection is a clear example. This review evaluates different aspects of the management of these infections.

Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign.

BACKGROUND: Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection. METHODS: Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. RESULTS: At presentation, most patients (94%) had > or =1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P<.001) and greater survival to 84 days (71% vs. 53%; P<.01) than did patients who presented with other imaging findings. CONCLUSIONS: Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.

Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.

Autotransfusion management during and after cardiopulmonary bypass alters fibrin degradation and transfusion requirements.

UNLABELLED: The coagulation-fibrinolytic profile during cardiopulmonary bypass (CPB) has been widely documented. However, less information is available on the possible persistence of these alterations when autotransfusion is used in management of perioperative blood loss. This study was designed to explore the influence of autotransfusion management on intravascular fibrin degradation and postoperative transfusions. Thirty patients, undergoing elective primary isolated coronary bypass grafting, were randomly allocated either to a control group (group A; n=15) or an intervention group (group B; n=15) in which mediastinal and residual CPB blood was collected and processed by a continuous autotransfusion system before re-infusion. Intravascular fibrin degradation as indicated by D-dimer generation was measured at five specific intervals and corrected for hemodilution. In addition, chest tube drainage and need for homologous blood were monitored. D-dimer generation increased significantly during CPB in group A, from 312 to 633 vs. 291 to 356 ng/mL in group B (p = .001). The unprocessed residual blood (group A) revealed an unequivocal D-dimer elevation, 4131 +/- 1063 vs. 279 +/- 103 ng/mL for the processed residual in group B (p < .001). Consequently, in the first post-CPB period, the intravascular fibrin degradation was significantly elevated in group A compared with group B (p = .001). Twenty hours postoperatively, no significant difference in D-dimer levels was detected between both groups. However, a significant intra-group D-dimer elevation pre- vs. postoperative was noticed from 312 to 828 ng/mL in group A and from 291 to 588 ng/mL in group B (p < .01 for both). Postoperative chest tube drainage was higher in the patients from group A, which also had the highest postoperative D-dimer levels. Patients in group A perceived a higher need for transfusions of red cells suspensions postoperatively. These data clearly indicate that autotransfusion management during and after CPB suppresses early postoperative fibrin degradation. KEYWORDS: cardiopulmonary bypass, cardiotomy suction, coronary surgery, autotransfusion, fibrin degradation.

Increasing fungal infections in the intensive care unit.

BACKGROUND: Yeasts and molds now rank among the most common pathogens in intensive care units. Whereas the incidence of Candida infections peaked in the late 1970s, aspergillosis is still increasing. METHOD: Review of the pertinent English-language literature. RESULTS: Most factors promoting an invasive fungal infection are difficult to avoid because they are connected directly to treatment of the underlying disease. Antifungal treatment is often commenced on an empiric basis, whereas it might be preferable to adopt a strategy based on a diagnostic procedure able to demonstrate or exclude fungal disease. Polyenes have been the drugs of choice, but voriconazole is the new standard for aspergillosis. For invasive candidiasis, fluconazole is a more convenient option, with the new echinocandins or voriconazole as alternatives. CONCLUSIONS: The incidence of invasive fungal infection is increasing, but so too are the choices of agents for therapy. For reasons of efficacy and safety, therapy with an echinocandin or azole antifungal agent is supplanting the use of polyenes.

Should the consensus guidelines' specific criteria for the diagnosis of invasive fungal infection be changed?

The introduction of a standardized set of criteria to define invasive fungal infections has fulfilled a need. The criteria make comparisons between various clinical studies more easy and facilitate discussions of trial designs. However, application of the criteria in practice has indicated that some criteria for possible disease (in particular, antibiotic-resistant fever during neutropenia) are rather unspecific and allow the inclusion of patients who are unlikely to have an invasive fungal infection in trials. On the other hand, new diagnostic tools have been validated sufficiently to consolidate the effect of the criteria on the diagnosis of invasive fungal infections. Finally, it has become evident that changing medical practices with deleterious consequences for the innate immune system extend the population at risk for invasive fungal infections. This combination of factors has urged researchers to reconsider the continuing appropriateness of the current definitions.

Forum report: issues in the design of trials of drugs for the treatment of invasive aspergillosis.

A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice.

Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients.

There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever.

Forum report: issues in the evaluation of diagnostic tests, use of historical controls, and merits of the current multicenter collaborative groups.

This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes required.

What are fungal infections?

Yeasts and moulds now rank amongst the 10 most frequently isolated pathogens in febrile patients with an impaired immune system. Fungi are mainly opportunistic pathogens that only invade the body if a severely weakened natural defense permits them to do so. Most factors facilitating an invasive fungal infection are unavoidable because they are directly connected to the underlying diseases as well as to their treatment.Modern aggressive treatment modalities jeopardize the defense mechanisms to an extent that even fungi with a low virulence may enter the body.