Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required

New resampling method for evaluating stability of clusters

<p>Abstract</p> <p>Background</p> <p>Hierarchical clustering is a widely applied tool in the analysis of microarray gene expression data. The assessment of cluster stability is a major challenge in clustering procedures. Statistical methods are required to distinguish between real and random clusters. Several methods for assessing cluster stability have been published, including resampling methods such as the bootstrap.</p> <p>We propose a new resampling method based on continuous weights to assess the stability of clusters in hierarchical clustering. While in bootstrapping approximately one third of the original items is lost, continuous weights avoid zero elements and instead allow non integer diagonal elements, which leads to retention of the full dimensionality of space, i.e. each variable of the original data set is represented in the resampling sample.</p> <p>Results</p> <p>Comparison of continuous weights and bootstrapping using real datasets and simulation studies reveals the advantage of continuous weights especially when the dataset has only few observations, few differentially expressed genes and the fold change of differentially expressed genes is low.</p> <p>Conclusion</p> <p>We recommend the use of continuous weights in small as well as in large datasets, because according to our results they produce at least the same results as conventional bootstrapping and in some cases they surpass it.</p

Кровесберегающий эффект транексамовой кислоты при протезировании коленного сустава

Objective: to evaluate the efficacy and safety of tranexamic acid in knee joint replacement. Subjects and methods: the prospective open-label study of the efficacy of tranexamic acid as an agent for blood loss reduction in knee joint replacement included 41 patients who were randomly randomized in two groups. Tranexamic acid (Tranexam, ZAO «Mir-Pharm») was injected intravenously in a dose of 15 mg/kg in Group 1 patients just before tourniquet removal, which caused a significant (p=0.003) reduction in drainage losses (from 556 (200; 800) ml to 234 (100; 300) ml) and in the calculated (from the changed concentration on days 3—4 postoperative days) values of overall blood loss (from 1821 (1348; 2156) ml to 1269 (924; 1580) ml (p=0.001) in the immediate postoperative period. There were no tranexamic acid-associated complications. Conclusion: Tranexamic acid is an effective agent in reducing blood loss when the knee joint is replaced. Key words: knee joint replacement, blood loss, tranexamic acid.Цель исследования . Оценка эффективности и безопасности транексамовой кислоты при протезировании коленного сустава. Материал и методы. В проспективное открытое исследование эффективности транексамовой кислоты, как средства уменьшения кровопотери при протезировании коленного сустава, включены 41 пациент, рандомизированно распределенные в две группы. Пациентам первой группы непосредственно перед снятием турникета внутривенно вводили транексамовую кислоту (Транексам, ЗАО «Мир-Фарм») в дозе 15 мг/кг, что привело в ближайшем послеоперационном периоде к достоверному (р=0,003) снижению объема дренажных потерь [с 556 (200; 800) мл до 234 (100; 300) мл] и расчетной (по изменению концентрации гемоглобина на 3—4-е сутки после операции) величины общей кровопотери (с 1821 (1348; 2156) мл до 1260 мл (924; 1580); р=0,001). Осложнений, связанных с применением транексамовой кислоты не было. Заключение. Транексамовая кислота является эффективным средством уменьшения кровопотери при протезировании коленного сустава. Ключевые слова: протезирование коленного сустава, кровопотеря, транексамовая кислота

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Some Calculable Contributions to Holographic Entanglement Entropy

Using the AdS/CFT correspondence, we examine entanglement entropy for a boundary theory deformed by a relevant operator and establish two results. The first is that if there is a contribution which is logarithmic in the UV cut-off, then the coefficient of this term is independent of the state of the boundary theory. In fact, the same is true of all of the coefficients of contributions which diverge as some power of the UV cut-off. Secondly, we show that the relevant deformation introduces new logarithmic contributions to the entanglement entropy. The form of some of these new contributions is similar to that found recently in an investigation of entanglement entropy in a free massive scalar field theory [1].Comment: 52 pages, no figure

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries

Objective To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. Study design In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. Results For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. Conclusions In most countries, mortality decreased whereas BPD increased for neonates born very preterm

Holographic Calculations of Renyi Entropy

We extend the approach of Casini, Huerta and Myers to a new calculation of the Renyi entropy of a general CFT in d dimensions with a spherical entangling surface, in terms of certain thermal partition functions. We apply this approach to calculate the Renyi entropy in various holographic models. Our results indicate that in general, the Renyi entropy will be a complicated nonlinear function of the central charges and other parameters which characterize the CFT. We also exhibit the relation between this new thermal calculation and a conventional calculation of the Renyi entropy where a twist operator is inserted on the spherical entangling surface. The latter insight also allows us to calculate the scaling dimension of the twist operators in the holographic models.Comment: 71 pages, 6 figure

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival