The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia.

INTRODUCTION: Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. METHODS: The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. RESULTS: Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. CONCLUSIONS: Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.

Expectations, Learning and Monetary Policy: An Overview of Recent Research

Expectations about the future are central for determination of current macroeconomic outcomes and the formulation of monetary policy. Recent literature has explored ways for supplementing the benchmark of rational expectations with explicit models of expectations formation that rely on econometric learning. Some apparently natural policy rules turn out to imply expectational instability of private agents’ learning. We use the standard New Keynesian model to illustrate this problem and survey the key results about interest-rate rules that deliver both uniqueness and stability of equilibrium under econometric learning. We then consider some practical concerns such as measurement errors in private expectations, observability of variables and learning of structural parameters required for policy. We also discuss some recent applications including policy design under perpetual learning, estimated models with learning, recurrent hyperinflations, and macroeconomic policy to combat liquidity traps and deflation.

New perspectives in the use of ink evidence in forensic science: Part I. Development of a quality assurance process for forensic ink analysis by HPTLC

The level of information provided by ink evidence to the criminal and civil justice system is limited. The limitations arise from the weakness of the interpretative framework currently used, as proposed in the ASTM 1422-05 and 1789-04 on ink analysis. It is proposed to use the likelihood ratio from the Bayes theorem to interpret ink evidence. Unfortunately, when considering the analytical practices, as defined in the ASTM standards on ink analysis, it appears that current ink analytical practices do not allow for the level of reproducibility and accuracy required by a probabilistic framework. Such framework relies on the evaluation of the statistics of the ink characteristics using an ink reference database and the objective measurement of similarities between ink samples. A complete research programme was designed to (a) develop a standard methodology for analysing ink samples in a more reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in a forensic context. This report focuses on the first of the three stages. A calibration process, based on a standard dye ladder, is proposed to improve the reproducibility of ink analysis by HPTLC, when these inks are analysed at different times and/or by different examiners. The impact of this process on the variability between the repetitive analyses of ink samples in various conditions is studied. The results show significant improvements in the reproducibility of ink analysis compared to traditional calibration methods.

Emergency department use by oldest-old patients from 2005 to 2010 in a Swiss university hospital.

BACKGROUND: Aging of the population in all western countries will challenge Emergency Departments (ED) as old patients visit these health services more frequently and present with special needs. The aim of this study is to describe the trend in ED visits by patients aged 85 years and over between 2005 and 2010, and to compare their service use to that of patients aged 65-84 years during this period and to investigate the evolution of these comparisons over time. METHODS: Data considered were all ED visits to the University of Lausanne Medical Center (CHUV), a tertiary Swiss teaching hospital, between 2005 and 2010 by patients aged 65 years and over (65+ years). ED visit characteristics were described according to age group and year. Incidence rates of ED visits and length of ED stay were calculated. RESULTS: Between 2005 and 2010, ED visits by patients aged 65 years and over increased by 26% overall, and by 46% among those aged 85 years and over (85+ years). Estimated ED visit incidence rate for persons aged 85+ years old was twice as high as for persons aged 65-84 years. Compared to patients aged 65-84 years, those aged 85+ years were more likely to be hospitalized and have a longer ED stay. This latter difference increased over time between 2005 and 2010. CONCLUSIONS: Oldest-old patients are increasingly using ED services. These services need to adapt their care delivery processes to meet the needs of a rising number of these complex, multimorbid and vulnerable patients.

The use of the likelihood ratio for evaluative and investigative purposes in comparative forensic handwriting examination

This paper extends previous research and discussion on the use of multivariate continuous data, which are about to become more prevalent in forensic science. As an illustrative example, attention is drawn here on the area of comparative handwriting examinations. Multivariate continuous data can be obtained in this field by analysing the contour shape of loop characters through Fourier analysis. This methodology, based on existing research in this area, allows one describe in detail the morphology of character contours throughout a set of variables. This paper uses data collected from female and male writers to conduct a comparative analysis of likelihood ratio based evidence assessment procedures in both, evaluative and investigative proceedings. While the use of likelihood ratios in the former situation is now rather well established (typically, in order to discriminate between propositions of authorship of a given individual versus another, unknown individual), focus on the investigative setting still remains rather beyond considerations in practice. This paper seeks to highlight that investigative settings, too, can represent an area of application for which the likelihood ratio can offer a logical support. As an example, the inference of gender of the writer of an incriminated handwritten text is forwarded, analysed and discussed in this paper. The more general viewpoint according to which likelihood ratio analyses can be helpful for investigative proceedings is supported here through various simulations. These offer a characterisation of the robustness of the proposed likelihood ratio methodology.

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.

Generating controlled image sets in cognitive neuroscience research.

The investigation of perceptual and cognitive functions with non-invasive brain imaging methods critically depends on the careful selection of stimuli for use in experiments. For example, it must be verified that any observed effects follow from the parameter of interest (e.g. semantic category) rather than other low-level physical features (e.g. luminance, or spectral properties). Otherwise, interpretation of results is confounded. Often, researchers circumvent this issue by including additional control conditions or tasks, both of which are flawed and also prolong experiments. Here, we present some new approaches for controlling classes of stimuli intended for use in cognitive neuroscience, however these methods can be readily extrapolated to other applications and stimulus modalities. Our approach is comprised of two levels. The first level aims at equalizing individual stimuli in terms of their mean luminance. Each data point in the stimulus is adjusted to a standardized value based on a standard value across the stimulus battery. The second level analyzes two populations of stimuli along their spectral properties (i.e. spatial frequency) using a dissimilarity metric that equals the root mean square of the distance between two populations of objects as a function of spatial frequency along x- and y-dimensions of the image. Randomized permutations are used to obtain a minimal value between the populations to minimize, in a completely data-driven manner, the spectral differences between image sets. While another paper in this issue applies these methods in the case of acoustic stimuli (Aeschlimann et al., Brain Topogr 2008), we illustrate this approach here in detail for complex visual stimuli.

Harmonization of research and control in schistosomiasis

I have been employed by several different organizations during over 30 years working on schistosomiasis, the majority spent in endemic areas of Caribean, South America, Africa and the Western Pacific. Much of the work is best classified as applied research but sometimes it strayed to the extremes of either public health control programmes or pure research. Over this period, there have been several significant research developments that have altered our whole approach to control. Ideally, research and control should complement each other but, in reality, they sometimes have conflicting objectives. Public health workers understandably wish to provide immediate, shot-term protection to the communities in their care, but research workers may, within ethical limits, reasonably want to observe untreated communities for extended periods in order to understand the underluing process of transmission, disease pathogenesis and immunity to help develop more effective control measures. An example of this situation has occured recently in Senegal where water development projects seem to have favoured the introduction and spreed of Schistosoma mansoni in the Senegal River Basin. I have been asked to be the scientific consultant to the newly formed ESPOIR programme, linking European research organizations and the Senegal Ministry of Health, to reconcile the conflictiong aims of public health workers, wishing to use whatever funds can be obtained for an immediate chemotherapy to try to eliminate the focus, at present confined to the vicinity of a relatively small, commercially run sugar irrigation scheme; and research workers who see a rare chance to study the development of immune mechanisms in a adults in a community not previously exposed to the infection. This information could prove invaluable in understanding the development of immunity and the pathogenesis of disease, leading eventually to the development of vaccines to revolutionise the future approach to schistosomiasis...

Adolescent's suicide attempts: populations at risk, vulnerability, and substance use.

Adolescence corresponds to a transition period that requires adaptation and change capacities and skills. Most young people succeed with this challenge, whereas a minority fail. In order to identify with the teenage culture, become autonomous, and differentiate from their parents, some adolescents choose to use drugs, beginning with the use of cigarettes, alcohol, cannabis, followed by other illicit drugs such as opiates and stimulants. A high proportion of these adolescents attempt suicide, which is the primary cause of death during adolescence in many European countries. Who are the "vulnerable" adolescents? What are the mechanisms that can explain the varieties of drug-use initiation or suicide attempts? Can "protective factors" be identified? What kind of strategies might be developed at a social and political level in order to prevent or to minimize drug abuse and suicide attempts, among other harmful behaviors? These issues will be discussed on the basis of the recent literature and in the light of a recent study carried out in the French-speaking part of Switzerland on large cohorts of adolescent drug users. Unresolved critical issues are noted and future needed research is suggested.

Quantitative ultrasound for the detection and management of osteoporosis.

Quantitative ultrasound (QUS) appears to be developing into an acceptable, low-cost and readily-accessible alternative to dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the detection and management of osteoporosis. Perhaps the major difficulty with their widespread use is that many different QUS devices exist that differ substantially from each other, in terms of the parameters they measure and the strength of empirical evidence supporting their use. But another problem is that virtually no data exist outside of Caucasian or Asian populations. In general, heel QUS appears to be most tested and most effective. Some, but not all heel QUS devices are effective assessing fracture risk in some, but not all populations, the evidence being strongest for Caucasian females > 55 years old, though some evidence exists for Asian females > 55 and for Caucasian and Asian males > 70. Certain devices may allow to estimate the likelihood of osteoporosis, but very limited evidence exists supporting QUS use during the initiation or monitoring of osteoporosis treatment. Likely, QUS is most effective when combined with an assessment of clinical risk factors (CRF); with DXA reserved for individuals who are not identified as either high or low risk using QUS and CRF. However, monitoring and maintenance of test and instrument accuracy, precision and reproducibility are essential if QUS devices are to be used in clinical practice; and further scientific research in non-Caucasian, non-Asian populations clearly is compulsory to validate this tool for more widespread use.

Biocurators and biocuration: surveying the 21st century challenges.

Curated databases are an integral part of the tool set that researchers use on a daily basis for their work. For most users, however, how databases are maintained, and by whom, is rather obscure. The International Society for Biocuration (ISB) represents biocurators, software engineers, developers and researchers with an interest in biocuration. Its goals include fostering communication between biocurators, promoting and describing their work, and highlighting the added value of biocuration to the world. The ISB recently conducted a survey of biocurators to better understand their educational and scientific backgrounds, their motivations for choosing a curatorial job and their career goals. The results are reported here. From the responses received, it is evident that biocuration is performed by highly trained scientists and perceived to be a stimulating career, offering both intellectual challenges and the satisfaction of performing work essential to the modern scientific community. It is also apparent that the ISB has at least a dual role to play to facilitate biocurators' work: (i) to promote biocuration as a career within the greater scientific community; (ii) to aid the development of resources for biomedical research through promotion of nomenclature and data-sharing standards that will allow interconnection of biological databases and better exploit the pivotal contributions that biocurators are making. DATABASE URL: http://biocurator.org.

Médicaments et grossesse : modifications pharmacocinétiques et place du suivi thérapeutique pharmacologique [Pharmacokinetic Alterations in Pregnancy and Use of Therapeutic Drug Monitoring].

Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency.

High altitude, a natural research laboratory for the study of cardiovascular physiology and pathophysiology.

High altitude constitutes an exciting natural laboratory for medical research. Although initially, the aim of high-altitude research was to understand the adaption of the organism to hypoxia and find treatments for altitude-related diseases, during the past decade or so, the scope of this research has broadened considerably. Two important observations led the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema represents a unique model that allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Second, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we will review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

On the use of IRMS in forensic science: proposals for a methodological approach.

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensicscience denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstratedits potential to distinguish chemically identical compounds coming from different sources. Despite thenumerous applications of IRMS to a wide range of forensic materials, its implementation in a forensicframework is less straightforward than it appears. In addition, each laboratory has developed its ownstrategy of analysis on calibration, sequence design, standards utilisation and data treatment without aclear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose amethodological framework of the whole process using IRMS methods. We emphasize the importance ofconsidering isotopic results as part of a whole approach, when applying this technology to a particularforensic issue. The process is divided into six different steps, which should be considered for a thoughtfuland relevant application. The dissection of this process into fundamental steps, further detailed, enablesa better understanding of the essential, though not exhaustive, factors that have to be considered in orderto obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratorycomparisons.