Light or Deep Pressure: Medical Staff Members Differ Extensively in Their Tactile Stimulation During Preterm Apnea

Background: Even though tactile stimulation is common practice to terminate preterm apnea, the style and intensity of these interventions is not specified during theoretical or practical training and has never been clinically evaluated. Objective: The present study was designed to analyze the various modes of tactile stimulation used to terminate preterm apnea and measure the pressure intensity and frequency of these stimulations. Methods: A model with the size and weight of an actual preterm infant was equipped with sensor technology to measure stimulation pressure and frequency of tactile stimulation. Additionally a camera system was used to record hand positions and stimulation modes. Seventy medical staff members took part in the experiment. Results: We found extreme between subjects differences in stimulation pressure that could not be explained by professional experience but, to a degree, depended on apnea intensity. Pressures ranged from 11.11 to 226.87 mbar during low intensity apnea and from 9.89 to 428.15 mbar during high intensity apnea. The majority of participants used rhythmic stimulation movements with a mean frequency of ∼1 Hz. Different modes (rubbing, squeezing, tickling, and tapping) and finger positions were used. Conclusion: Medical staff members intuitively adjust their tactile stimulation pressure depending on the premature infants’ apnea intensity. However, mean pressure values varied greatly between subjects, with similar pressure ranges for low and high intensity apnea. The question remains which pressure intensities are necessary or sufficient for the task. It is reasonable to assume that some stimulation types may be more effective in rapidly terminating an apneic event

Caspase-mediated cleavage of raptor participates in the inactivation of mTORC1 during cell death.

The mammalian target of rapamycin complex 1 (mTORC1) is a highly conserved protein complex regulating key pathways in cell growth. Hyperactivation of mTORC1 is implicated in numerous cancers, thus making it a potential broad-spectrum chemotherapeutic target. Here, we characterized how mTORC1 responds to cell death induced by various anticancer drugs such rapamycin, etoposide, cisplatin, curcumin, staurosporine and Fas ligand. All treatments induced cleavage in the mTORC1 component, raptor, resulting in decreased raptor-mTOR interaction and subsequent inhibition of the mTORC1-mediated phosphorylation of downstream substrates (S6K and 4E-BP1). The cleavage was primarily mediated by caspase-6 and occurred at two sites. Mutagenesis at one of these sites, conferred resistance to cell death, indicating that raptor cleavage is important in chemotherapeutic apoptosis

Elective high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: an individual patient data meta-analysis

<p>Abstract</p> <p>Background</p> <p>Despite the considerable amount of evidence from randomized controlled trials and meta-analyses, uncertainty remains regarding the efficacy and safety of high-frequency oscillatory ventilation as compared to conventional ventilation in the early treatment of respiratory distress syndrome in preterm infants. This results in a wide variation in the clinical use of high-frequency oscillatory ventilation for this indication throughout the world. The reasons are an unexplained heterogeneity between trial results and a number of unanswered, clinically important questions. Do infants with different risk profiles respond differently to high-frequency oscillatory ventilation? How does the ventilation strategy affect outcomes? Does the delay – either from birth or from the moment of intubation – to the start of high-frequency oscillation modify the effect of the intervention? Instead of doing new trials, those questions can be addressed by re-analyzing the individual patient data from the existing randomized controlled trials.</p> <p>Methods/Design</p> <p>A systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of the original individual data from each infant included in each randomized controlled trial addressing this question.</p> <p>The study objective is to estimate the effect of high-frequency oscillatory ventilation on the risk for the combined outcome of death or bronchopulmonary dysplasia or a severe adverse neurological event. In addition, it will explore whether the effect of high-frequency oscillatory ventilation differs by the infant's risk profile, defined by gestational age, intrauterine growth restriction, severity of lung disease at birth and whether or not corticosteroids were given to the mother prior to delivery. Finally, it will explore the importance of effect modifying factors such as the ventilator device, ventilation strategy and the delay to the start of high-frequency ventilation.</p> <p>Discussion</p> <p>An international collaborative group, the PreVILIG Collaboration (Prevention of Ventilator Induced Lung Injury Group), has been formed with the investigators of the original randomized trials to conduct this systematic review. In the field of neonatology, individual patient data meta-analysis has not been used previously. Final results are expected to be available by the end of 2009.</p

Climate Change Accuracy: Observing Requirements and Economic Value

No abstract availabl

Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas.

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH-derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-κB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR-related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlation with presenting clinical features nor significant impact on survival was observed, the presence of TCR-related mutations correlated with early disease progression. Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas

Nabelvenenkatheter- und periphere zentrale katheterassoziierte Komplikationen bei Frühgeborenen mit einem Geburtsgewicht < 1250 g : Ergebnisse einer Umfrage in Österreich und Deutschland

Background and objective Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight < 1250 g and associated rates of catheter-related adverse events. Methods Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). Results In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1–10 days were bacterial infection: 4.2 ± 3.4% (range 0–10%); thrombosis: 7.3 ± 7.1% (0–20%); emboli: 0.9 ± 2.0% (0–5%); organ injury: 1.1 ± 1.9% (0–5%); cardiac arrhythmia: 2.2 ± 2.5% (0–5%); and dislocation: 5.4 ± 8.7% (0–30%); and for PICCs with a dwell time of 1–14 days bacterial infection: 15.0 ± 3.4% (range 2.5–30%); thrombosis; 4.3 ± 3.5% (0–10%); emboli: 0.8 ± 1.6% (0–5%); organ injury: 1.5 ± 2.3% (0–5%); cardiac arrhythmia: 1.5 ± 2.3% (0–5%), and dislocation: 8.5 ± 4.6% (0–30%). Conclusion The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.Hintergrund und Ziel Nabelvenenkatheter („umbilical venous catheters“ [UVC]) und periphere zentrale Venenkatheter (PICC) werden häufig bei Frühgeborenen eingesetzt, sind jedoch mit einer Reihe von schwerwiegenden Komplikationen verbunden. In Österreich und Deutschland wurde eine Umfrage durchgeführt, um die Verwendung von UVC und PICC bei Frühgeborenen mit einem Geburtsgewicht < 1250 g und die damit verbundenen Raten von katheterbedingten unerwünschten Ereignissen zu bewerten. Methoden Elektronische Befragung der teilnehmenden Zentren der NeoVitaA-Studie. Hauptergebnisparameter waren die gemeldeten Raten von UVC- und PICC-assoziierten Komplikationen (Infektion, Thrombose, Embolie, Organverletzung, Arrhythmie, Dislokation, Sonstiges). Ergebnisse Insgesamt wurden 20 neonatale Intensivstationen (NICU) mit maximaler Intensivpflege in Österreich und Deutschland (Level I) kontaktiert, wobei 12/20 (60 %) von leitenden Neonatologen beantwortet wurden. Die gemeldeten Raten für UVC mit einer Verweildauer von 1 bis 10 Tagen waren bakterielle Infektionen: 4,2 ± 3,4 % (Bereich: 0–10 %); Thrombose: 7,3 ± 7,1 % (0–20 %); Embolie: 0,9 ± 2,0 % (0–5 %); Organverletzung: 1,1 ± 1,9 % (0–5 %); Herzrhythmusstörungen: 2,2 ± 2,5 % (0–5 %); und Dislokation: 5,4 ± 8,7% (0–30 %); und bei PICC mit einer Verweildauer von 1 bis 14 Tagen bakterielle Infektionen: 15,0 ± 3,4 % (Bereich: 2,5–30 %); Thrombose: 4,3 ± 3,5 % (0–10 %); Embolie: 0,8 ± 1,6 % (0–5 %); Organverletzung: 1,5 ± 2,3 % (0–5 %); Herzrhythmusstörungen: 1,5 ± 2,3 % (0–5 %) und Verrenkungen: 8,5 ± 4,6 % (0–30 %). Schlussfolgerung Die in dieser Umfrage berichteten katheterbedingten Komplikationsraten unterschieden sich zwischen UVC und PICC und waren höher als die in der Literatur berichteten. Um zuverlässigere Daten zu diesem klinisch wichtigen Thema zu erhalten, ist eine große prospektive, multizentrische, randomisierte, kontrollierte Studie geplant, in der die Nichtunterlegenheit einer verlängerten UVC-Verweildauer (bis zu 10 Tage) gegenüber dem frühen Wechsel (bis zu 5 Tage) zu einem PICC untersucht werden soll

Climate Change Observation Accuracy: Requirements and Economic Value

This presentation will summarize a new quantitative approach to determining the required accuracy for climate change observations. Using this metric, most current global satellite observations struggle to meet this accuracy level. CLARREO (Climate Absolute Radiance and Refractivity Observatory) is a new satellite mission designed to resolve this challenge is by achieving advances of a factor of 10 for reflected solar spectra and a factor of 3 to 5 for thermal infrared spectra. The CLARREO spectrometers can serve as SI traceable benchmarks for the Global Satellite Intercalibration System (GSICS) and greatly improve the utility of a wide range of LEO and GEO infrared and reflected solar satellite sensors for climate change observations (e.g. CERES, MODIS, VIIIRS, CrIS, IASI, Landsat, etc). A CLARREO Pathfinder mission for flight on the International Space Station is included in the U.S. President"TM"s fiscal year 2016 budget, with launch in 2019 or 2020. Providing more accurate decadal change trends can in turn lead to more rapid narrowing of key climate science uncertainties such as cloud feedback and climate sensitivity. A new study has been carried out to quantify the economic benefits of such an advance and concludes that the economic value is ~ $9 Trillion U.S. dollars. The new value includes the cost of carbon emissions reductions