1,721,033 research outputs found

    Congenital cytomegalovirus infection : hearing prospects and antiviral strategies : dreamscapes of clarity

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    With a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide. Accounting for 21% of the sensorineural hearing loss (SNHL) at birth and 25% of the SNHL by the age of four years, cCMV is an important cause of non-hereditary congenital and late-onset hearing loss. Once present, the hearing loss can deteriorate or improve over the years which requires long-term audiological follow-up. The prevalence and characteristics of cCMV-related hearing loss have already been described though risk factors for hearing loss remain unclear. By analysing data of the Flemish CMV registry, we found that children with petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Moreover, children with a first trimester infection were also at higher risk to develop late-onset hearing loss. In contrast, children with a third trimester seroconversion had a limited risk to develop late-onset hearing loss which led to a targeted audiological follow-up program. We recommend to cease audiological follow-up if normal hearing is found at the age of one year in children with a third trimester seroconversion. Clinicians can use these novel findings to counsel parents about the risk of cCMV-related hearing loss. For decades, antiviral therapy with (val)ganciclovir has been offered to children with moderate to severe symptoms at birth. We performed a systematic review to assess the effect of (val)ganciclovir on hearing outcome but it was difficult to draw firm conclusions due to the low-quality design of the included studies and high heterogeneity between the included studies. Consequently, the effect of valganciclovir on long-term hearing outcome remains unclear and treatment duration (a six-week or six-month therapy) is still a matter of debate. Therefore, we performed a quasi-randomized trial investigating the effect of (val)ganciclovir on hearing outcome at the age of four years or older. To equate the risk of spontaneous hearing evolution, treated and untreated children were matched for known risk factors of spontaneous hearing evolution. In our study, (val)ganciclovir did not result in more hearing improvement or less hearing deterioration. In contrast, a six-week therapy prevented late-onset hearing loss. Comparing a six-week to a six-month therapy, we found no additional benefit of prolonging therapy to six months. These findings can aid in treatment decision making and hopefully initiate a critical revision by clinicians and researchers to consider a six-month therapy as a future research topic instead of a beneficial standard care. Systemic therapy with (val)ganciclovir is associated with side-effects. Fundamental and translational research might aid in optimization of the treatment protocol. Murine inner ear research was initiated at our centre to implement a murine model of cCMV-related hearing loss. This will enable us to investigate the feasibility of local drug delivery into the inner ear and learn more about the pathophysiology in the near future. This research project has gathered new insights into cCMV-related hearing prospects and antiviral strategies. To further explore risk factors for cCMV-related hearing loss, it would be interesting to investigate the importance of viral strain, viral load, host/viral genetic profile, and host inflammatory response. We believe that insights into the pathophysiology of cCMV-related hearing loss could aid in current understanding, estimation of hearing outcome, and targeted therapies. Although our studies were based on the largest database worldwide, a larger sample size is needed to tackle current limitations. Future studies investigating the effect of valganciclovir in asymptomatic children and investigating therapeutic effect on long-term neurological outcome are needed

    Eosinophilic mucin in chronic rhinosinusitis : clinical implications and long-term outcome

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    Chronic rhinosinusitis (CRS) is a complex, heterogeneous and prevalent disorder involving the nasal and paranasal mucosae. It has long been categorized by clinical phenotype, mainly CRS without versus with nasal polyps (CRSsNP and CRSwNP respectively). This distinction also proved important in estimating the success rate of surgical therapy, demonstrating a higher risk of recurrence in CRSwNP. In a 3-year prospective follow-up study of CRS patients after endoscopic sinus surgery, we found a recurrence rate of 8.8% in CRSsNP (n=125) versus 39.6% in CRSwNP (n=96). Given these findings, we more closely looked at the CRSwNP group (n=196) in a subsequent long-term prospective follow-up study after surgery. Here, the recurrence rate gradually increased over time up to 62% after 10 years. Thorough pathophysiological research in primary CRS added a novel distinction, namely allergic, eosinophilic and non-eosinophilic airway inflammation. This distinction enabled a shift from clinical phenotyping towards cellular endotyping with different inflammatory types and biomarkers. This is of utmost importance in the development and implementation of novel treatment options, such as biologicals. The latter are considered based on clinical needs, in which persistence of disease after classic therapy plays an important role. We already included mucosal tissue and secretion analysis in our follow-up studies, of whom the first even started in January 2003. In the 3-year follow-up study, more positive eosinophil counts (>5 per high power field) were observed in CRSwNP compared to CRSsNP (78.1% versus 42.4% respectively). The presence of eosinophilic mucin and fungal hyphae was also higher in CRSwNP compared to CRSsNP. If we related this to recurrence in CRSsNP, it was mainly observed in the subgroup with a positive eosinophil count and the presence of eosinophilic mucin (23.8%). These patients demonstrated an endotype that is mainly seen in CRSwNP although they do not have nasal polyps (yet). In CRSwNP, a difference in recurrence rate was observed in patients with a negative eosinophil count (9.5%) versus a positive eosinophil count (48.0%). This number even increased to 72.7% when eosinophilic mucin and fungal hyphae were demonstrated on histopathology. In the 10-year follow-up study of CRSwNP patients, we could confirm the presence of eosinophilic mucin as a predictive factor of worse outcome (73.2% versus 39.2% recurrence in presence and absence of eosinophilic mucin respectively). Given the concept of united airways, linking the upper and lower airways as an interconnected system sharing the same inflammatory responses, the prevalence of asthma was also determined. Of the included CRSwNP patients, 27.8% had asthma at inclusion, whereas another 17.3% developed asthma during follow-up. Their recurrence numbers could be linked to the different asthma groups: 48% of patients without asthma developed CRSwNP recurrence, compared to 81% for the group of asthma at inclusion and 74% for the group of asthma developed during follow-up. Consequently, a link of eosinophilic disease, named a type 2 inflammatory response, and recurrent disease, need for revision surgery and a higher risk of and aggravation of asthma could be established. The above-mentioned studies highlighted the importance of local tissue and secretion analysis in endotyping CRS patients, which proved highly predictive for disease outcome. Current guidelines mainly forward tissue analysis obtained by biopsy or during surgery. In a subsequent study, we compared the histopathological results of two techniques for sinonasal secretion sampling (nasal blown secretions and endoscopic aspiration, preoperatively collected) with the operative tissue analysis as the gold standard (n=53). Nasal aspiration sampling demonstrated a higher sensitivity to detect type 2 inflammation compared to nasal blown secretions (85.4% versus 31.7% respectively), and both had a specificity of 100%. We also looked at reproducibility, which was 90% for both eosinophil and neutrophil presence in nasal aspiration sampling over different time points in the same patients (n=20, half of whom with type 2 inflammation). The different laboratory staining techniques were elaborated, including haematoxylin and eosin staining, Congo red staining and Gomori methenamine silver staining. In conclusion, we were able to demonstrate the importance of local tissue and secretion analysis in predicting the CRS outcome after endoscopic sinus surgery. The presence of local eosinophils and eosinophilic mucin, pointing towards a type 2 inflammatory type, is related to a higher recurrence rate. Not only local CRS recurrence was observed in these patients, but also the development of asthma was significantly higher. We further showed the potential of sinonasal secretion sampling in determining the inflammatory endotype. Aspiration and analysis of sinonasal secretions is a simple, cheap and well-tolerated technique with very good sensitivity and reproducibility, and excellent specificity. We proposed a structured analysis for histopathology in endotyping CRS, including different staining techniques. With this, clinicians can endotype their patients even before surgery as not all patients will undergo surgery given the effectiveness of biologicals. We might even hypothesize a role for sinonasal secretion analysis in the accuracy and follow-up evaluation of novel biologicals

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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