Observations of middle atmospheric H2O and O3 during the 2010 major sudden stratospheric warming by a network of microwave radiometers

In this study, we present middle atmospheric water vapor (H2O) and ozone (O3) measurements obtained by ground-based microwave radiometers at three European locations in Bern (47° N), Onsala (57° N) and Sodankylä (67° N) during Northern winter 2009/2010. In January 2010, a major sudden stratospheric warming (SSW) occurred in the Northern Hemisphere whose signatures are evident in the ground-based observations of H2O and O3. The observed anomalies in H2O and O3 are mostly explained by the relative location of the polar vortex with respect to the measurement locations. The SSW started on 26 January 2010 and was most pronounced by the end of January. The zonal mean temperature in the middle stratosphere (10 hPa) increased by approximately 25 Kelvin within a few days. The stratospheric vortex weakened during the SSW and shifted towards Europe. In the mesosphere, the vortex broke down, which lead to large scale mixing of polar and midlatitudinal air. After the warming, the polar vortex in the stratosphere split into two weaker vortices and in the mesosphere, a new, pole-centered vortex formed with maximum wind speed of 70 m s−1 at approximately 40° N. The shift of the stratospheric vortex towards Europe was observed in Bern as an increase in stratospheric H2O and a decrease in O3. The breakdown of the mesospheric vortex during the SSW was observed at Onsala and Sodankylä as a sudden increase in mesospheric H2O. The following large-scale descent inside the newly formed mesospheric vortex was well captured by the H2O observations in Sodankylä. In order to combine the H2O observations from the three different locations, we applied the trajectory mapping technique on our H2O observations to derive synoptic scale maps of the H2O distribution. Based on our observations and the 3-D wind field, this method allows determining the approximate development of the stratospheric and mesospheric polar vortex and demonstrates the potential of a network of ground-based instruments.

Pathogenesis of pulmonary edema: learning from high-altitude pulmonary edema

Pulmonary edema is a problem of major clinical importance resulting from a persistent imbalance between forces that drive water into the airspace of the lung and the biological mechanisms for its removal. Here, we will review the fundamental mechanisms implicated in the regulation of alveolar fluid homeostasis. We will then describe the perturbations of pulmonary fluid homeostasis implicated in the pathogenesis of pulmonary edema in conditions associated with increased pulmonary capillary pressure, namely cardiogenic pulmonary edema and high-altitude pulmonary edema (HAPE), with particular emphasis on the latter that has provided important new insight into underlying mechanisms of pulmonary edema. We will provide evidence that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent a central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction, and, in turn, capillary stress failure and alveolar fluid flooding. We will then demonstrate that exaggerated pulmonary hypertension, while possibly a prerequisite, may not always be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we will outline, how this new insight gained from studies in HAPE, may be translated into the management of pulmonary edema and hypoxemia related disease states in general.

When language of instruction and language of application differ: Cognitive costs of bilingual mathematics learning

Bilingual education programs implicitly assume that the acquired knowledge is represented in a language-independent way. This assumption, however, stands in strong contrast to research findings showing that information may be represented in a way closely tied to the specific language of instruction and learning. The present study aims to examine whether and to which extent cognitive costs appear during arithmetic learning when language of instruction and language of retrieving differ. Thirty-nine high school students participating in a bilingual education program underwent a four-day training on multiplication and subtraction problems in one language (German or French), followed by a test session in which they had to solve trained as well as untrained problems in both languages. We found that cognitive costs related to language switching appeared for both arithmetic operations. Implications of our findings are discussed with respect to bilingual education as well as to cognitive mechanisms underlying different arithmetic operations.

Personalized Tuning of a Reinforcement Learning Control Algorithm for Glucose Regulation

Artificial pancreas is in the forefront of research towards the automatic insulin infusion for patients with type 1 diabetes. Due to the high inter- and intra-variability of the diabetic population, the need for personalized approaches has been raised. This study presents an adaptive, patient-specific control strategy for glucose regulation based on reinforcement learning and more specifically on the Actor-Critic (AC) learning approach. The control algorithm provides daily updates of the basal rate and insulin-to-carbohydrate (IC) ratio in order to optimize glucose regulation. A method for the automatic and personalized initialization of the control algorithm is designed based on the estimation of the transfer entropy (TE) between insulin and glucose signals. The algorithm has been evaluated in silico in adults, adolescents and children for 10 days. Three scenarios of initialization to i) zero values, ii) random values and iii) TE-based values have been comparatively assessed. The results have shown that when the TE-based initialization is used, the algorithm achieves faster learning with 98%, 90% and 73% in the A+B zones of the Control Variability Grid Analysis for adults, adolescents and children respectively after five days compared to 95%, 78%, 41% for random initialization and 93%, 88%, 41% for zero initial values. Furthermore, in the case of children, the daily Low Blood Glucose Index reduces much faster when the TE-based tuning is applied. The results imply that automatic and personalized tuning based on TE reduces the learning period and improves the overall performance of the AC algorithm.

Improvement of antibiotic prescription in outpatient care: a cluster-randomized intervention study using a sentinel surveillance network of physicians.

OBJECTIVES To assess the effectiveness of implementing guidelines, coupled with individual feedback, on antibiotic prescribing behaviour of primary care physicians in Switzerland. METHODS One hundred and forty general practices from a representative Swiss sentinel network of primary care physicians participated in this cluster-randomized prospective intervention study. The intervention consisted of providing guidelines on treatment of respiratory tract infections (RTIs) and uncomplicated lower urinary tract infections (UTIs), coupled with sustained, regular feedback on individual antibiotic prescription behaviour during 2 years. The main aims were: (i) to increase the percentage of prescriptions of penicillins for all RTIs treated with antibiotics; (ii) to increase the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics; (iii) to decrease the percentage of quinolone prescriptions for all cases of exacerbated COPD (eCOPD) treated with antibiotics; and (iv) to decrease the proportion of sinusitis and other upper RTIs treated with antibiotics. The study was registered at ClinicalTrials.gov (NCT01358916). RESULTS While the percentage of antibiotics prescribed for sinusitis or other upper RTIs and the percentage of quinolones prescribed for eCOPD did not differ between the intervention group and the control group, there was a significant increase in the percentage of prescriptions of penicillins for all RTIs treated with antibiotics [57% versus 49%, OR = 1.42 (95% CI 1.08-1.89), P = 0.01] and in the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics [35% versus 19%, OR = 2.16 (95% CI 1.19-3.91), P = 0.01] in the intervention group. CONCLUSIONS In our setting, implementing guidelines, coupled with sustained individual feedback, was not able to reduce the proportion of sinusitis and other upper RTIs treated with antibiotics, but increased the use of recommended antibiotics for RTIs and UTIs, as defined by the guidelines.

Time-course of "off-line" prefrontal rTMS effects--a PET study.

Low-frequency "off-line" repetitive transcranial magnetic stimulation (rTMS) over the course of several minutes has attained considerable attention as a research tool in cognitive neuroscience due to its ability to induce functional disruptions of brain areas. This disruptive rTMS effect is highly valuable for revealing a causal relationship between brain and behavior. However, its influence on remote interconnected areas and, more importantly, the duration of the induced neurophysiological effects, remain unknown. These aspects are critical for a study design in the context of cognitive neuroscience. In order to investigate these issues, 12 healthy male subjects underwent 8 H(2)(15)O positron emission tomography (PET) scans after application of long-train low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC). Immediately after the stimulation train, regional cerebral blood flow (rCBF) increases were present under the stimulation site as well as in other prefrontal cortical areas, including the ventrolateral prefrontal cortex (VLPFC) ipsilateral to the stimulation site. The mean increases in rCBF returned to baseline within 9 min. The duration of this unilateral prefrontal rTMS effect on rCBF is of particular interest to those who aim to influence behavior in cognitive paradigms that use an "off-line" approach.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Trajectory mapping of middle atmospheric water vapor by a mini network of NDACC instruments

The important task to observe the global coverage of middle atmospheric trace gases like water vapor or ozone usually is accomplished by satellites. Climate and atmospheric studies rely upon the knowledge of trace gas distributions throughout the stratosphere and mesosphere. Many of these gases are currently measured from satellites, but it is not clear whether this capability will be maintained in the future. This could lead to a significant knowledge gap of the state of the atmosphere. We explore the possibilities of mapping middle atmospheric water vapor in the Northern Hemisphere by using Lagrangian trajectory calculations and water vapor profile data from a small network of five ground-based microwave radiometers. Four of them are operated within the frame of NDACC (Network for the Detection of Atmospheric Composition Change). Keeping in mind that the instruments are based on different hardware and calibration setups, a height-dependent bias of the retrieved water vapor profiles has to be expected among the microwave radiometers. In order to correct and harmonize the different data sets, the Microwave Limb Sounder (MLS) on the Aura satellite is used to serve as a kind of traveling standard. A domain-averaging TM (trajectory mapping) method is applied which simplifies the subsequent validation of the quality of the trajectory-mapped water vapor distribution towards direct satellite observations. Trajectories are calculated forwards and backwards in time for up to 10 days using 6 hourly meteorological wind analysis fields. Overall, a total of four case studies of trajectory mapping in different meteorological regimes are discussed. One of the case studies takes place during a major sudden stratospheric warming (SSW) accompanied by the polar vortex breakdown; a second takes place after the reformation of stable circulation system. TM cases close to the fall equinox and June solstice event from the year 2012 complete the study, showing the high potential of a network of ground-based remote sensing instruments to synthesize hemispheric maps of water vapor.

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

OBJECTIVES Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. METHODS Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) ≥0.4) and occurrence of IAC during a 4-week period. RESULTS Within 4 weeks after inclusion a CCI ≥0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1, -2, -3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI ≥0.4. Similarly, none of the analyzed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p = 0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. CONCLUSION Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.

Trajectory mapping of middle atmospheric water vapor by a mini network of NDACC instruments

The important task to observe the global coverage of middle atmospheric trace gases like water vapor or ozone usually is accomplished by satellites. Climate and atmospheric studies rely upon the knowledge of trace gas distributions throughout the stratosphere and mesosphere. Many of these gases are currently measured from satellites, but it is not clear whether this capability will be maintained in the future. This could lead to a significant knowledge gap of the state of the atmosphere. We explore the possibilities of mapping middle atmospheric water vapor in the Northern Hemisphere by using Lagrangian trajectory calculations and water vapor profile data from a small network of five ground-based microwave radiometers. Four of them are operated within the frame of NDACC (Network for the Detection of Atmospheric Composition Change). Keeping in mind that the instruments are based on different hardware and calibration setups, a height-dependent bias of the retrieved water vapor profiles has to be expected among the microwave radiometers. In order to correct and harmonize the different data sets, the Microwave Limb Sounder (MLS) on the Aura satellite is used to serve as a kind of traveling standard. A domain-averaging TM (trajectory mapping) method is applied which simplifies the subsequent validation of the quality of the trajectory-mapped water vapor distribution towards direct satellite observations. Trajectories are calculated forwards and backwards in time for up to 10 days using 6 hourly meteorological wind analysis fields. Overall, a total of four case studies of trajectory mapping in different meteorological regimes are discussed. One of the case studies takes place during a major sudden stratospheric warming (SSW) accompanied by the polar vortex breakdown; a second takes place after the reformation of stable circulation system. TM cases close to the fall equinox and June solstice event from the year 2012 complete the study, showing the high potential of a network of ground-based remote sensing instruments to synthesize hemispheric maps of water vapor.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial

INTRODUCTION Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.