Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. RESULTS: We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. CONCLUSION: SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease

A new method to analyse the pace of child development: Cox regression validated by a bootstrap resampling procedure

<p>Abstract</p> <p>Background</p> <p>Various perinatal factors influencing neuromotor development are known from cross sectional studies. Factors influencing the age at which distinct abilities are acquired are uncertain. We hypothesized that the Cox regression model might identify these factors.</p> <p>Methods</p> <p>Neonates treated at Aachen University Hospital in 2000/2001 were identified retrospectively (n = 796). Outcome data, based on a structured interview, were available from 466 children, as were perinatal data. Factors possibly related to outcome were identified by bootstrap selection and then included into a multivariate Cox regression model. To evaluate if the parental assessment might change with the time elapsed since birth we studied five age cohorts of 163 normally developed children.</p> <p>Results</p> <p>Birth weight, gestational age, congenital cardiac disease and periventricular leukomalacia were related to outcome in the multivariate analysis (p < 0.05). Analysis of the control cohorts revealed that the parents' assessment of the ability of bladder control is modified by the time elapsed since birth.</p> <p>Conclusions</p> <p>Combined application of the bootstrap resampling procedure and multivariate Cox regression analysis effectively identifies perinatal factors influencing the age at which distinct abilities are acquired. These were similar as known from previous cross sectional studies. Retrospective data acquistion may lead to a bias because the parental memories change with time. This recommends applying this statistical approach in larger prospective trials.</p

Suggesting Software Measurement Plans with unsupervised learning data analysis

International audienceSoftware measurement processes require to consider more and more data, measures and metrics. Measurement plans become complex, time and resource consuming, considering diverse kinds of software project phases. Experts in charge of defining the measurement plans have to deal with management and performance constraints to select the relevant metrics. They need to take into account a huge number of data though distributed processes. Formal models and standards have been standardized to facilitate some of these aspects. However, the maintainability of the measurements activities is still constituted of complex activities. In this paper, we aim at improving our previous work, which aims at reducing the number of needed software metrics when executing measurement process and reducing the expertise charge. Based on unsupervised learning algorithm, our objective is to suggest software measurement plans at runtime and to apply them iteratively. For that purpose, we propose to generate automatically analysis models using unsupervised learning approach in order to efficiently manage the efforts, time and resources of the experts. An implementation has been done and integrated on an industrial platform. Experiments are processed to show the scalability and effectiveness of our approach. Discussions about the results have been provided. Furthermore, we demonstrate that the measurement process performance could be optimized while being effective , more accurate and faster with reduced expert interventio

The Formation of Inflation Perceptions – Some Empirical Facts for European Countries: some empirical facts for European countries

This paper investigates how households form their perceptions of consumer price inflation. Using data from the harmonized EU consumer survey, we find that inflation perceptions are inefficient and highly heterogeneous, yet contemporaneously related to the actual rate of inflation. Consequently, we estimate how often households update their beliefs employing Carroll's (2003) epidemiological model. Our results indicate that inflation perceptions are generally less responsive to new information than expectations. Unlike studies on expectations, we cannot confirm that a constant fraction of the population updates information every month. Also, the cross-sectional heterogeneity of perceptions is higher than implied by infrequent updating alone

The Formation of Inflation Perceptions – Some Empirical Facts for European Countries

This paper presents some empirical facts on the dynamics of perceived inflation rates for EU countries. First, we find that perceptions are inefficient and highly heteroge- neous, yet contemporaneously related to the actual rate of inflation. Second, similar to studies on inflation expectations, we estimate how often European consumers up- date their inflation perceptions employing Carroll's (2003) epidemiological model. The advantage of employing perceived instead of expected inflation is that the value of the newest information can exactly be measured: the actual rate of inflation. Our findings indicate that the stickiness of perceptions is generally higher than the stick- iness of expectations. Unlike studies using expectations, however, we cannot confirm that a constant fraction of the population updates information every month. Also observed heterogeneity of perceptions is much higher than implied by the epidemio- logical model.perceived inflation, sticky information, inattention, expectation formation

Automated suggesting software metrics framework

International audienceDue to the complexity of the current software, the measurement processes become crucial activities. However, due to the quantity of aspects to be measured, the software measurement plans are heavy to manage. It leads to very complex measurement plans engendering eventual losses of time and performance. The main objective of our paper is the improvement of the measurement plans by making the metrics use more flexible. This is an important requirements for the project managers. This allows to tackle specific useful metrics in avoiding measures that are not always relevant during an identified measured period of time. We propose to analyze and classify the measurements at runtime using a learning approach (Support Vector Machine, SVM) in order to define the relevant metrics that should be used at a specific time t. We designed a suggestion process that selects metrics from a current measurement plan or reorient (suggest) that measurement plan by proposing to execute other metrics. We implemented our framework on an efficient platform and successfully ran several experiments that we discuss and commen

Modeling OMG SMM metrics using the Modelio modeling tool in the MEASURE project

International audienceMost software system properties can be quantified with the application of measurement processes. OMG's Structured Metrics Meta-Model (SMM) supports the meta-model agnostic method to define these measurements. This paper introduces the first building block of the MEASURE (Measuring Software Engineering) [5] project tool chain: the Modelio modeling tool together with the SMM Module developed based in Modelio's open source distribution. These tools permit the formal specification of metrics and a common interchange format enabling interoperability between the project's tools. This paper presents this new approach of metrics specification that simplifies their combination and their integration into compliant platforms and tool

CD151 gene and protein expression provides independent prognostic information for patients with adenocarcinoma of the esophagus and gastroesophageal junction treated by esophagectomy

Background. Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis.Methods. Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx)-naive patients with external validation in a separate cohort of 62 CRTx-naive patients and 169 patients with advanced-stage disease treated with CRTx.Results. As a novel prognostic biomarker after external validation, CD151 showed promise. Patients exhibiting high levels of CD151 (>= median) had a longer median overall survival than patients with low CD151 tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox-regression model with adjustment for tumor stage [adjusted hazard ratio (aHR), 0.33; 95 % confidence interval (CI), 0.14-0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR, 0.22; 95 % CI, 0.08-0.59; p = 0.003). This effect was not found in the separate cohort of CRTx-exposed patients.Conclusion. Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone