Variation in Current Management of Term and Late-preterm Neonates at Risk for Early-onset Sepsis: An International Survey and Review of Guidelines.

BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

Multiparametric magnetic resonance imaging of the prostate: current concepts

Multiparametric MR (mpMR) imaging is rapidly evolving into the mainstay in prostate cancer (PCa) imaging. Generally, the examination consists of T2-weighted sequences, diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) evaluation, and less often proton MR spectroscopy imaging (MRSI). Those functional techniques are related to biological properties of the tumor, so that DWI correlates to cellularity and Gleason scores, DCE correlates to angiogenesis, and MRSI correlates to cell membrane turnover. The combined use of those techniques enhances the diagnostic confidence and allows for better characterization of PCa. The present article reviews and illustrates the technical aspects and clinical applications of each component of mpMR imaging, in a practical approach from the urological standpoint.

Comparison of standardized uptake values measured on 18F-NaF PET/CT scans using three different tube current intensities

Objective: To analyze standardized uptake values (SUVs) using three different tube current intensities for attenuation correction on 18FNaF PET/CT scans. Materials and Methods: A total of 254 18F-NaF PET/CT studies were analyzed using 10, 20 and 30 mAs. The SUVs were calculated in volumes of interest (VOIs) drawn on three skeletal regions, namely, right proximal humeral diaphysis (RH), right proximal femoral diaphysis (RF), and first lumbar vertebra (LV1) in a total of 712 VOIs. The analyses covered 675 regions classified as normal (236 RH, 232 RF, and 207 LV1). Results: Mean SUV for each skeletal region was 3.8, 5.4 and 14.4 for RH, RF, and LV1, respectively. As the studies were grouped according to mAs value, the mean SUV values were 3.8, 3.9 and 3.7 for 10, 20 and 30 mAs, respectively, in the RH region; 5.4, 5.5 and 5.4 for 10, 20 and 30 mAs, respectively, in the RF region; 13.8, 14.9 and 14.5 for 10, 20 and 30 mAs, respectively, in the LV1 region. Conclusion: The three tube current values yielded similar results for SUV calculation.

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

Solitary pulmonary nodule and 18F-FDG PET/CT. Part 2: accuracy, cost-effectiveness, and current recommendations

Abstract A solitary pulmonary nodule is a common, often incidental, radiographic finding. The investigation and differential diagnosis of solitary pulmonary nodules remain complex, because there are overlaps between the characteristics of benign and malignant processes. There are currently many strategies for evaluating solitary pulmonary nodules. The main objective is to identify benign lesions, in order to avoid exposing patients to the risks of invasive methods, and to detect cases of lung cancer accurately, in order to avoid delaying potentially curative treatment. The focus of this study was to review the evaluation of solitary pulmonary nodules, to discuss the current role of 18F-fluorodeoxyglucose positron-emission tomography, addressing its accuracy and cost-effectiveness, and to detail the current recommendations for the examination in this scenario.

Extracorporeal support for pulmonary resection: current indications and results.

Extracorporeal assistances are exponentially used for patients, with acute severe but reversible heart or lung failure, to provide more prolonged support to bridge patients to heart and/or lung transplantation. However, experience of use of extracorporeal assistance for pulmonary resection is limited outside lung transplantation. Airways management with standard mechanical ventilation system may be challenging particularly in case of anatomical reasons (single lung), presence of respiratory failure (ARDS), or complex tracheo-bronchial resection and reconstruction. Based on the growing experience during lung transplantation, more and more surgeons are now using such devices to achieve good oxygenation and hemodynamic support during such challenging cases. We review the different extracorporeal device and attempt to clarify the current practice and indications of extracorporeal support during pulmonary resection.

Towards a Network Government? A critical analysis of current assessment methods for e-Government

Contemporary public administrations have become increasingly more complex, having to cordinate actions with emerging actors in the public and the private spheres. In this scenario the modern ICTs have begun to be seen as an ideal vehicle to resolve some of the problems of public administration. We argue that there is a clear need to explore the extent to which public administrations are undergoing a process of transformation towards a netowork government linked to the systematic incorporation of ICTs in their basic activities. Through critically analysing a selection of e-government evaluation reports, we conclude that research should be carried out if we are to build a solid government assessment framework based on network-like organisation characteristics.

Electrical characteristics of eddy current position sensor

In the thesis the principle of work of eddy current position sensors and the main cautions that must be taken into account while sensor design process are explained. A way of automated eddy current position sensor electrical characteristics measurement is suggested. A prototype of the eddy current position sensor and its electrical characteristics are investigated. The results obtained by means of the automated measuring system are explained.

Evolutionary Ecology of Mountain Birch in Subarctic Stress Gradients: Interplay of Biotic and Abiotic Factors in Plant-Plant Interactions and Evolutionary Processes

In nature, variation for example in herbivory, wind exposure, moisture and pollution impact often creates variation in physiological stress and plant productivity. This variation is seldom clear-cut, but rather results in clines of decreasing growth and productivity towards the high-stress end. These clines of unidirectionally changing stress are generally known as ‘stress gradients’. Through its effect on plant performance, stress has the capacity to fundamentally alter the ecological relationships between individuals, and through variation in survival and reproduction it also causes evolutionary change, i.e. local adaptations to stress and eventually speciation. In certain conditions local adaptations to environmental stress have been documented in a matter of just a few generations. In plant-plant interactions, intensities of both negative interactions (competition) and positive ones (facilitation) are expected to vary along stress gradients. The stress-gradient hypothesis (SGH) suggests that net facilitation will be strongest in conditions of high biotic and abiotic stress, while a more recent ‘humpback’ model predicts strongest net facilitation at intermediate levels of stress. Plant interactions on stress gradients, however, are affected by a multitude of confounding factors, making studies of facilitation-related theories challenging. Among these factors are plant ontogeny, spatial scale, and local adaptation to stress. The last of these has very rarely been included in facilitation studies, despite the potential co-occurrence of local adaptations and changes in net facilitation in stress gradients. Current theory would predict both competitive effects and facilitative responses to be weakest in populations locally adapted to withstand high abiotic stress. This thesis is based on six experiments, conducted both in greenhouses and in the field in Russia, Norway and Finland, with mountain birch (Betula pubescens subsp. czerepanovii) as the model species. The aims were to study potential local adaptations in multiple stress gradients (both natural and anthropogenic), changes in plant-plant interactions under conditions of varying stress (as predicted by SGH), potential mechanisms behind intraspecific facilitation, and factors confounding plant-plant facilitation, such as spatiotemporal, ontogenetic, and genetic differences. I found rapid evolutionary adaptations (occurring within a time-span of 60 to 70 years) towards heavy-metal resistance around two copper-nickel smelters, a phenomenon that has resulted in a trade-off of decreased performance in pristine conditions. Heavy-metal-adapted individuals had lowered nickel uptake, indicating a possible mechanism behind the detected resistance. Seedlings adapted to heavy-metal toxicity were not co-resistant to others forms of abiotic stress, but showed co-resistance to biotic stress by being consumed to a lesser extent by insect herbivores. Conversely, populations from conditions of high natural stress (wind, drought etc.) showed no local adaptations, despite much longer evolutionary time scales. Due to decreasing emissions, I was unable to test SGH in the pollution gradients. In natural stress gradients, however, plant performance was in accordance with SGH, with the strongest host-seedling facilitation found at the high-stress sites in two different stress gradients. Factors confounding this pattern included (1) plant size / ontogenetic status, with seedling-seedling interactions being competition dominated and host-seedling interactions potentially switching towards competition with seedling growth, and (2) spatial distance, with competition dominating at very short planting distances, and facilitation being strongest at a distance of circa ¼ benefactor height. I found no evidence for changes in facilitation with respect to the evolutionary histories of plant populations. Despite the support for SGH, it may be that the ‘humpback’ model is more relevant when the main stressor is resource-related, while what I studied were the effects of ‘non-resource’ stressors (i.e. heavy-metal pollution and wind). The results have potential practical applications: the utilisation of locally adapted seedlings and plant facilitation may increase the success of future restoration efforts in industrial barrens as well as in other wind-exposed sites. The findings also have implications with regard to the effects of global change in subarctic environments: the documented potential by mountain birch for rapid evolutionary change, together with the general lack of evolutionary ‘dead ends’, due to not (over)specialising to current natural conditions, increase the chances of this crucial forest-forming tree persisting even under the anticipated climate change.