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Pre-packed columns have been increasingly used in process development and biomanufacturing thanks to their ease of use and consistency. Traditionally, packing quality is predicted through rate models, which require extensive calibration efforts through independent experiments to determine relevant mass transfer and kinetic rate constants. Here we propose machine learning as a complementary predictive tool for column performance. A machine learning algorithm, extreme gradient boosting, was applied to a large data set of packing quality (plate height and asymmetry) for pre-packed columns as a function of quantitative parameters (column length, column diameter, and particle size) and qualitative attributes (backbone and functional mode). The machine learning model offered excellent predictive capabilities for the plate height and the asymmetry (90 and 93%, respectively), with packing quality strongly influenced by backbone (∼70% relative importance) and functional mode (∼15% relative importance), well above all other quantitative column parameters. The results highlight the ability of machine learning to provide reliable predictions of column performance from simple, generic parameters, including strategic qualitative parameters such as backbone and functionality, usually excluded from quantitative considerations. Our results will guide further efforts in column optimization, for example, by focusing on improvements of backbone and functional mode to obtain optimized packings.

FallberichtEin 20-jähriger adipöser Patient stellte sich im August 2018 in einer auswärtigen Klinik zur Septumplastik und Muschelverkleinerung bei Septumdeviation und Muschelhyperplasie ohne relevante Vorerkrankungen vor. Intraoperativ war keine Antibiotikagabe erfolgt. Postoperativ wurde der Patient zur weiteren Betreuung mit Doyle-Splinten und Gelaspon® auf die Normalstation verlegt. Es war Hochsommer und die Krankenzimmertemperatur bei ausgefallener Klimaanlage sehr hoch. Wie erst später fremdanamnestisch bekannt wurde, hatte der Patient eine bereits vor stationärer Aufnahme mehrere Tage bestehende, aber nicht mitgeteilte Enteritis. Am Morgen des ersten postoperativen Tages wies der Patient Zeichen der Sepsis auf: arterielle Hypotonie, Tachykardie, Tachypnoe und Desorientierung (= quick Sepsis – related organ failure assessment Score [qSOFA Score] = positiv). Es erfolgte die Gabe von Kristalloiden und bei Schwellung des Gesichtes die Entfernung der Doyle-Splinte. Ungeachtet dessen kam es zur progredienten Verschlechterung und Entwicklung eines schweren Schocks, so dass mit der Gabe von Vasopressoren begonnen wurde. Bei zusätzlich beginnender respiratorischer Erschöpfung wurde die Indikation zur Intubation gestellt. Während der Intubation kam es zur Aspiration. Zur weiteren intensivmedizinischen Versorgung erfolgte aus kapazitären Gründen die Verlegung auf die interdisziplinäre internistische Intensivstation unserer Klinik mit zunächst unklarem Infektfokus. Bei Übernahme war der Patient intubiert und beatmet (CPAP PEEP 9 mbar, Druckunterstützung 16 mbar, FiO2 0,8) und hoch katecholaminpflichtig (Noradrenalin 1 µg/kg/min, Epinephrin 0,2 µg/kg/min).

Purpose Chronic obstructive pulmonary disease (COPD) is a risk factor for acquiring multiple drug resistant bacteria. The main objective of this analysis was to question a beneficial outcome in the routine use of antipseudomonal antibiotics in the empiric treatment of severe AECOPD in Intensive Care Unit patients. Material and methods We report a retrospective, observational cohort study in adult patients with severe AECOPD admitted to ICU at a tertiary care university hospital. Antibiotic treatment on admission as well as microbiology samples were analyzed. The influence of SOFA score at admission, age, sex and antibiotic choice upon survival was investigated by multivariable analysis. Results 437 patients were included. Mean age was 68 years (±10), 46.5% were female. 271/437 patients (62%) were initially treated with antibiotics covering Pseudomonas aeruginosa. Overall, positive microbiology samples were found in 107 patients (24.5%). P. aeruginosa was only found in 3.7%. There was no significant difference in 30-day ICU mortality after adjusting for age, sex and severity of illness (20.4% ± 11.6 in patients with Pseudomonas inactive antibiotics versus 29.3% ± 10.8 in patients with PAA, p=0.113). Conclusions Empiric use of antipseudomonal antibiotics did not result in improved ICU survival in this retrospective analysis.

In order to understand the extent to which airborne PFAS emission can impact soil and groundwater, we conducted a sampling campaign in areas of conserved forest lands near Bennington, VT/Hoosick Falls, NY. This has been home to sources of PFAS air-emissions from Teflon-coating operations for over 50 years. Since 2015, the Vermont and New York Departments of Environmental Conservation have documented ∼1200 residential wells and two municipal water systems across a 200 km2 area contaminated with perfluorooctanoic acid (PFOA). Given the large areal extent of the plume, and the fact that much of the contaminated area lies up-gradient and across rivers from manufactures, we seek to determine if groundwater contamination could have resulted primarily from air-emission, land deposition, and subsequent leaching to infiltrating groundwater. Sampling of soils and groundwater in the Green Mountain National Forest (GMNF) downwind of factories shows that both soil and groundwater PFOA contamination extend uninterrupted from inhabited areas into conserved forest lands. Groundwater springs and seeps in the GMNF located 8 km downwind, but300 meters vertically above factories, contain up to 100 ppt PFOA. Our results indicate that air-emitted PFAS can contaminate groundwater and soil in areas outside of those normally considered down-gradient of a source with respect to regional groundwater flow.

Glutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF).This was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298).In total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7-11.1 mg/dL; glutamine: 0.2-3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1-9.6; post-filter 0.95 mg/dL IQR 0.5-2; p 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6-1; post-filter 0.2 mg/dL IQR 0-0.2; p 0.001).In this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.

Ein 20-jähriger adipöser Patient stellte sich im August 2018 in einer auswärtigen Klinik zur Septumplastik und Muschelverkleinerung bei Septumdeviation und Muschelhyperplasie ohne relevante Vorerkrankungen vor. Intraoperativ war keine Antibiotikagabe erfolgt. Postoperativ wurde der Patient zur weiteren Betreuung mit Doyle-Splinten und Gelaspon

Temperature control improves neurological prognosis in comatose cardiac arrest (CA) survivors. Previous reports demonstrate that most affected patients show signs of significant systemic inflammation. In an effort to better characterize potential temperature-related effects on key inflammatory pathways, we investigate the course of Tryptophan (Trp) levels, Tryptophan catabolites (including kynurenines) and indoleamine-2,3-dioxygenase (IDO)-activity in post CA patients.In an observational blinded endpoint analysis, a total of n=270 serial samples from 20 post CA patients (63.1±16.6 yrs., 45% shockable rhythm, mean time to return of spontaneous circulation (ROSC) 26.6±16.0min) treated with target temperature management (TTM) were analyzed. Core body temperatures, course of Trp, Trp catabolites (incl. kynurenines), and estimated IDO-activity were followed up for a maximum of 7 days after ROSC. Patients were followed up until hospital discharge or death and functional outcome was recorded.Over the 7-day observational interval, marked changes in Trp serum levels and IDO-activity were noted. In general, Trp serum levels but not IDO-activity seemed to parallel with the course of core body temperature. In explorative analyses, a correlation of Trp (rho=0.271 (95%-CI: 0.16-0.38, p0.0001) and IDO-activity (rho=-0.155, 95%-CI: -0.27 to -0.037, p=0.01) with core body temperature was observed. Linear mixed effect models revealed a positive significant association of core body temperature with Trp serum levels (Likelihood ratio test χ(2)=6.35, p=0.012). In patients with good (vs. unfavorable) outcome, a tendency toward higher Trp serum levels, lower IDO-activity, and lower Kynurenic acid levels was noted.We observed significant changes in Trp catabolism and IDO-activity that appeared temperature associated in post CA patients. Under hypothermia, decreased serum levels of Trp and increased IDO-activity were noted. We speculate from our data that IDO-induction during hypothermia contributes to the previously described increased susceptibility to infection or sepsis under reduced temperatures.

We present a training procedure and a T-maze equipped with sensors and automated feeders for training spatial behavioral tasks in rodents. The maze can be transformed from an enclosed box to a maze of variable dimensions. The modularity of the protocol and setup makes it highly flexible and suitable for training a wide variety of spatial tasks, and facilitates incremental training stages of increasing maze size for more efficient learning. The apparatus, in its software and hardware, is able to adapt to animal performance, adjusting task challenges and difficulty.Two different methods of automatic behavioral scoring are evaluated against manual methods. Sensors embedded in the maze provide information regarding the order of reward locations visited and the time between the activation of the cue via the nose-poke and the activation of the reward location sensors. The distributions of these reaction times differ between correct and incorrect trials, providing an index of behavior and motivation. The automated maze system allows the trainer to operate and monitor the task away from the experimental set-up, minimizing human interference and improving the reproducibility of the experiment. We show that our method succeeds in training a binary forced-choice task in rats.

Background: Transiently increased transaminases is a common finding after cardiac arrest but little is known about the functional liver capacity (LiMAx) during the post-cardiac arrest syndrome and treatment in the intensive care unit (ICU). The aim of this trial was to evaluate liver function capacity in post-cardiac arrest survivors undergoing targeted temperature management (TTM) in ICU. Methods: Thirty-two post-cardiac arrest survivors were prospectively included with all patients undergoing TTM at 33 degrees C for 24 hours. Blood samples were collected, and LiMAx testing was performed at days 1, 2, 5, and 10 post-cardiac arrest. LiMAx is a non-invasive, in vivo, dynamic breath test determining cytochrome P450 1A2 (CYP1A2) capacity using intravenous (IV) C-13-methacetin, thus reflecting maximum liver function capacity. Static liver parameters were determined and compared to LiMAx values. Results: A typical pattern of transiently, mildly increased transaminases was demonstrated without fulfilling the criteria for hypoxic hepatitis (HH). CYP1A2 activity was reduced with slow normalization over 10 days (lowest median 48 hours after cardiac arrest: 228.5 (25-75 percentile 105.2-301.7 mu g/kg/h, P < .05). Parameters reflecting the liver synthetic function were not impaired, as assessed by, in standard laboratory testing. Conclusion: Liver functional capacity is impaired in patients after cardiac arrest undergoing TTM at 33 degrees C. More data are needed to determine if liver functional capacity may add relevant information, especially in the context of pharmacotherapy, to individualize post-cardiac arrest care.

In 2012, UNM teamed up with the Gardner Institute for Excellence in Undergraduate Education, to conduct a Foundations of Excellence® (FoE) First College Year Self Study addressing student success. As members of the First Year Steering Committee, we invented, coordinated, measured, and documented programs for linking students to the academic experiences and support that were best attuned to their needs.

In this paper, we present the design, modeling, fabrication and initial wafer level characterization of Capacitive Micromachined Ultrasound Transducers (CMUTs) with target operating frequencies suitable for medical imaging and therapy. Using finite element analysis, a multilayer stack of thin film materials for the hexagonal shaped cell membrane was studied. An optimized stack in terms of membrane stress and cell size was selected for device fabrication based on a wafer bonding approach. The modelling, fabrication and characterization are treated within this paper.

It is an uninformative truism to state that the brain operates at multiple spatial and temporal scales, each with each own set of emergent phenomena. More worthy of attention is the point that our current understanding of it cannot clearly indicate which of these phenomenological scales are the significant contributors to the brain’s function and primary output (i.e. behaviour). Apart from the sheer complexity of the problem, a major contributing factor to this state of affairs is the lack of instrumentation that can simultaneously address these multiple scales without causing function altering damages to the underlying tissue. One important facet of this problem is that standard neural recording devices normally require one output connection per electrode. This limits the number of electrodes that can fit along the thin shafts of implantable probes generating a limiting balance between density and spread. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density probes.Here we report the design and in-vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes; the outcome of the European research project NeuroSeeker. We show that this design targets both local and global spatial scales by allowing the simultaneous recording of more than 1000 neurons spanning 7 functional regions with a single shaft. The neurons show similar recording longevity and signal to noise ratio to passive probes of comparable size and no adverse effects in awake or anesthetized animals. Addressing the data management of this device we also present novel visualization and monitoring methods. Using the probe with freely moving animals we show how accessing a number of cortical and subcortical brain regions offers a novel perspective on how the brain operates around salient behavioural events. Finally, we compare this probe with lower density, non CMOS designs (which have to adhere to the one electrode per output line rule). We show that an increase in density results in capturing neural firing patterns, undetectable by lower density devices, which correlate to self-similar structures inherent in complex naturalistic behaviour.To help design electrode configurations for future, even higher density, CMOS probes, recordings from many different brain regions were obtained with an ultra-dense passive probe.

We report on the reduced spectral diffusion of nitrogen vacancy centers in waveguides and cavities. We also design a cavity that provides both high quality factor and isolation from diamond surfaces.

© 2017 IEEE. Non-classical light sources, such as atoms and atom-like emitters play central roles in many areas of quantum information processing with applications as single photon generators, sources for nonlinearity and quantum memories. Solid-state quantum emitters have attracted growing interest due to the promise of combining remarkable optical properties with the convenience of scalability [1]. In recent years, there has been tremendous progress in developing quantum emitter systems based on crystallographic defects in wide-bandgap semiconductors. Nitrogen vacancies (NV) in diamond were among the first studied systems due to the well-defined optical transitions as well as electronic spin states that can be controlled optically. Quantum spins in diamond are among the most advanced systems in solid state for quantum based technologies such as quantum computing or quantum sensing [2]. Nevertheless, solid-state quantum emitters are not only limited to diamond and efforts to engineer single photon emitters (SPE) based on atom-like defects in scalable system have expanded beyond NV centers in diamond. Similar quantum emitters have been discovered in many other wide-bandgap host materials, including silicon carbide (SiC), III-nitride semiconductors such as gallium nitride (GaN) and aluminum nitride (AlN), and layered materials such as hexagonal boron nitride (hBN) [1]. Here, we will review our recent progress in developing and characterizing new quantum emitters in wide-bandgap semiconductors, and consider their applications as quantum light sources and sensors.

Aim Prognosis after cardiac arrest in the era of modern critical care is still poor with a high mortality of approximately 90%. Around 30% of the survivors have neurological impairments. Targeted temperature management (TTM) is the only treatment option which can improve mortality and neurological outcome. It is so far unclear if bleeding complications occur more often in patients undergoing TTM treatment. Methods We conducted a systematic literature research in September 2013 including three major databases i.e. MEDLINE, EMBASE and CENTRAL. All studies were rated in respect to the ILCOR Guidelines and concerning their level of evidence and quality. We then performed a meta-analysis on bleeding disposition under TTM. Results We initially found 941 studies out of which 34 matched our requirements and were thus included in our overview. Five studies including 599 patients were summarized in a meta-analysis concerning bleeding complications of all severities. There was a trend toward higher bleeding in patients treated with TTM (RR: 1.30, 95% CI: 0.97–1.74) which did not reach significance ( p =0.085). Seven studies with an overall 599 patients were included in our meta-analysis on bleeding requiring transfusion. There was no significant difference in the incidence of severe bleeding with a risk ratio of 0.97 (95% CI: 0.61–1.56, p =0.909). Conclusions The data included in our meta-analysis indicate that, concerning the risk of bleeding, TTM is a safe method for patients after cardiac arrest. We did not observe a significantly higher risk for bleeding in patients undergoing TTM.

Introduction Non-invasive near-infrared spectroscopy (NIRS) offers the possibility to determine regional cerebral oxygen saturation (rSO 2 ) in patients with cardiac arrest. Limited data from recent studies indicate a potential for early prediction of neurological outcome. Methods Sixty cardiac arrest patients were prospectively enrolled, 22 in-hospital cardiac arrest (IHCA) and 38 out-of-hospital cardiac arrest (OHCA) patients respectively. NIRS of frontal brain was started after return of spontaneous circulation (ROSC) during admission to ICU and was continued until normothermia. Outcome was determined at ICU discharge by the Pittsburgh Cerebral Performance Category (CPC) and 6 months after cardiac arrest. Results A good outcome (CPC 1–2) was achieved in 23 (38%) patients, while 37 (62%) had a poor outcome (CPC 3–5). Patients with good outcome had significantly higher rSO 2 levels (CPC 1–2: rSO 2 68%; CPC 3–5: rSO 2 58%; p 2 within the first 24h period was 66% and 59% respectively and for the following 16h period 68% and 59% ( p 2 below a critical threshold of rsO 2 =50% within the first 40h yielded 70% specificity and 86% sensitivity for poor outcome. Conclusion On average, rSO 2 within the first 40h after ROSC is significantly lower in patients with poor outcome, but rSO 2 ranges largely overlap between outcome groups. Our data indicate limited potential for prediction of poor outcome by frontal brain rSO 2 measurements.

A listener’s capacity to discriminate between sounds is related to the amount of acoustic variability that exists between these sounds. However, a full understanding of how this natural variability impacts neural activity and behavior is lacking. Here, we tested monkeys’ ability to discriminate between different utterances of vocalizations from the same acoustic class (i.e., coos and grunts), while neural activity was simultaneously recorded in the anterolateral belt region (AL) of the auditory cortex, a brain region that is a part of a pathway that mediates auditory perception. Monkeys could discriminate between coos better than they could discriminate between grunts. We also found AL activity was more informative about different coos than different grunts. This difference could be attributed, in part, to our finding that coos had more acoustic variability than grunts. Thus, intrinsic acoustic variability constrained the discriminability of AL spike trains and the ability of rhesus monkeys to discriminate between vocalizations.

Out-of-hospital cardiac arrest is a frequent cause of death in Europe. Hypoxic ischemic encephalopathy (HIE) often develops in initial survivors, and the question of treatment limitation arises in severely affected patients. To establish a poor prognosis with a high level of certainty, the use of a combination of prognostic parameters such as neurological examination, somatosensory evoked potentials, and neuron-specific enolase is common practice. A few recent studies suggest that gray–white matter ratio (GWR) determined from cranial computed tomography (CT) scans is an additional reliable predictor of poor prognosis. The standard GWR determination method involves measurements of 16 different regions of interest (ROIs). We tested whether a simplified method to obtain GWR has equivalent reliability for poor outcome prediction. We retrospectively analyzed 98 patients after cardiac arrest who had been treated with hypothermia. CT scans were obtained within the first 7 days after cardiac arrest. Neurological outcome was determined at intensive care unit discharge. Four different methods to obtain GWR were compared in a receiver-operating characteristic curve analysis with respect to their prognostic value for poor outcome prediction. The simplest method using only four ROIs (putamen and internal capsule bilaterally) had the same prognostic value compared with the standard method using 16 ROIs. The simplified GWR predicted poor outcome with a sensitivity of 44 % at 100 % specificity. Our results indicate that for poor outcome prediction in survivors of cardiac arrest, a simplified GWR determination is feasible and has the same reliability as the complex standard procedure.

Background Noninvasive regional cerebral oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) might inform on extent and duration of cerebral hypoxia during cardiopulmonary resuscitation (CPR). This information may be used to guide resuscitation efforts and may carry relevant early prognostic information. Methods We prospectively investigated non-traumatic out-of-hospital cardiac arrest (OHCA) patients on scene. NIRS was started either during CPR or shortly after (

The production costs of micro systems are strongly correlated to the involved packaging technologies like wafer bonding. Well-established wafer bonding technologies need to be optimized to ensure the functionality and reliability of these micro systems. The requirements on this technologies regarding hermiticity, electrical contact, mechanical and thermal resistance are high. Typical wafer bonding technologies are anodic or direct wafer bonding using surface activation or such with intermediate layers like solder materials, polymers, glass layers or pure metal layers. The bonding process is defined by parameters like temperature, tool pressure, hermeticity and substrate properties (surface quality, device surface patterning), the used intermediate layer and the device dimensions. Glass frit bonding is a cost-effective, industry related wafer bonding technology with intermediate layers manufactured by screen printing. This technology provides hermeticity without high demands regarding surface quality and allows lateral electrical interconnects through the bonding interface. However, conditions like high process temperature in the range between 400°C and 500°C, the dielectric properties of the resulting bond frames and high bond frame width often prevent a footprint reduction of the microsystems. As an alternative, wafer bonding processes using pure metal intermediate layers manufactured by physical vapour deposition or electrochemical deposition can reduce the bond frame width. However, typical bonding conditions are high process temperatures in the range between 300°C and 500°C and high bonding pressures up to 800 MPa, assumed that a high surface quality is given. With the usage of metallic nano particles, both bonding temperature and pressure can be dramatically reduced. In addition, demands on surface properties are low and the potential for 3D-integration on chip and wafer level is high. If the pore size after sintering is small enough, a hermetic bond could be enabled. The intermediate layers can be deposited using printing processes like screen printing or aerosol jet printing. This work will give an overview regarding state of the art approaches, describes capabilities of the additive material transfer technologies aerosol jet printing and screen printing with the purpose of intermediate layers manufactured for chip or wafer level bonding (see Figure 1). For realization of these applications, the deposition process and the related material morphology, the bonding with nano particle based intermediate layers as well as the characterization methods are described. Screen printed SnAgCu and Au micro- and nanoparticle intermediate layer were used to bond Au and Cu metallized wafers. The bonding experiments are performed using Cu and Au plated 6” silicon, as well as glass wafer in a standard wafer bonder. Different adhesion layers, layer thicknesses, as well as process parameters (pressure, atmosphere and bonding time) and their influences on the resulting bonding strength are investigated. The bonding capability using different widths of bonding frames on structured wafers is evaluated. The interface between nano particles and substrate was investigated. For bonding result evaluation, bonding frames and occurring bonding interfaces were analysed using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and focused ion beam (FIB). Mechanical properties were qualified using compression shear tests and tensile tests. Our results and international publications shows that successful bonds are possible by direct printed sub-micron Au and SnAgCu intermediate layers. But it is not possible to create hermetic bonds because the pore size is too high or flux is needed to obtain an oxide-free surface. An alternative is to use the so-called fluxless soldering, using gaeous flux (formic acid). Increasing bonding pressure correlates to higher tensile strength for the sintered bond frames. Compared to glass frit bonding, the sub-micron Au particle interface enables 3 times higher bond strength at bonding temperatures as low as 200°C. Grain growth and densification could be enhanced by increased bonding pressure. Results are strongly related to the printed pattern morphology. The process is capable to be adapted to chip level or can be expanded to 3D integration applications. Not only process-related costs could be saved, but also new possibilities could be realized, like metallization of MEMS at stages of manufacturing, where no wet chemical processes, no electroplating or no lithography steps are suitable anymore. Figure 1

Target temperature management (TTM) after cardiac arrest (CA) improves outcome in patients with acute coronary syndrome (ACS). Previous data point to an interaction between hypothermia and drug metabolism, potentially impacting on platelet function in patients on antiplatelet therapy.To compare clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with TTM (33°C, n=15) and in ACS patients (troponin positive) without TTM (n=18).Platelet function was measured by multiple electrode platelet aggregometry (MEA), light transmittance aggregometry (LTA) and VASP analysis before and after administration of a 600mg clopidogrel loading dose. Plasma levels of clopidogrel and its metabolites were measured. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. TTM was carried out for 24h at a target temperature of 33°C using a computer feedback surface cooling device in cardiac arrest patients.Plasma concentration of clopidogrel and metabolites was lower in the TTM group after 2 and 4h, respectively (all p0.005 vs. controls), and platelet function tests revealed an attenuated response to clopidogrel with respect to baseline platelet activity in the TTM group. This was significant for MEA, LTA and VASP analysis (all p0.05). Moreover, there was no significant difference in genotype and platelet function determined ex vivo at 33 or 37°C, respectively.Inhibition of platelet function is significantly lessened in TTM at 33°C, likely due to reduced clopidogrel absorption. Patients with TTM might thus have a higher risk for further cardiovascular events despite antiplatelet therapy with clopidogrel.

Background: Mild therapeutic hypothermia (MTH) improves outcome for patients with acute coronary syndrome (ACS) after cardiac arrest (CA). Previous data point to an interaction between hypothermia and drug metabolism, thus potentially impacting on platelet function under antiplatelet therapy. Purpose: The aim of the study is to determine clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with mild hypothermia (33°C, n=12) compared with ACS patients (troponin positive) with normal body temperature (n=14). Methods: Platelet function was measured by light transmittance aggregometry (LTA), multiple electrode platelet aggregometry (MEA) and VASP phosphorylation analysis before, 2h, 4h and 24h after administration of a 600 mg clopidogrel loading dose. Furthermore, plasma concentrations of clopidogrel, the active thiol metabolite and the inactive carboxyl metabolite were determined. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. Mild hypothermia was carried out according to current guidelines for 24 hours at a target temperature of 33°C. Results: Plasma concentration of clopidogrel and metabolites were lower in the MTH group after 2h and 4h, respectively (all pex vivo with 33°C and 37°C, respectively. Conclusion: Inhibition of platelet function is decreased under MTH, presumably due to a diminished clopidogrel absorption and metabolization. Thus, these patients might have a higher risk for cardiovascular events despite antiplatelet therapy.

Portfolios have been used in other fields for some time as a way to document development of competence and knowledge. Recently, the field of recreation and leisure studies has promoted the use of p...

We report on the fabrication of single-crystal diamond photonic crystal nanocavities coupled the diamond nitrogen vacancy center. We discuss techniques to realize cavity-coupled NV centers with coherence times exceeding 100 microseconds.

Objective Choline is related to phospholipid metabolism and is a marker for global ischaemia with a small reference range in healthy volunteers. The aim of our study was to characterize the early kinetics of plasma free choline in patients after cardiac arrest. Additionally, we investigated the potential of plasma free choline to predict neurological outcome. Methods Twenty patients admitted to our medical intensive care unit were included in this prospective, observational trial. All patients were enrolled between May 2010 and May 2011. They received post cardiac arrest treatment including mild therapeutic hypothermia which was initiated with a combination of cold fluid and a feedback surface cooling device according to current guidelines. Sixteen blood samples per patient were analysed for plasma free choline levels within the first week after resuscitation. Choline was detected by liquid chromatography-tandem mass spectrometry. Results Most patients showed elevated choline levels on admission (median 14.8 µmol/L; interquartile range; IQR 9.9-20.1) which subsequently decreased. 48 hours after cardiac arrest choline levels in all patients reached subnormal levels at a median of 4.0 µmol/L (IQR 3-4.9; p = 0.001). Subsequently, choline levels normalized within seven days. There was no significant difference in choline levels when groups were analyzed in relation to neurological outcome. Conclusions Our data indicate a choline deficiency in the early postresucitation phase. This could potentially result in impaired cell membrane recovery. The detailed characterization of the early choline time course may aid in planning of choline supplementation trials. In a limited number of patients, choline was not promising as a biomarker for outcome prediction.

Oscillatory activity in sensory cortices reflects changes in local excitation–inhibition balance, and recent work suggests that phase signatures of ongoing oscillations predict the perceptual detection of subsequent stimuli. Low-frequency oscillations are also entrained by dynamic natural scenes, suggesting that the chance of detecting a brief target depends on the relative timing of this to the entrained rhythm. We tested this hypothesis in humans by implementing a cocktail-party-like scenario requiring subjects to detect a target embedded in a cacophony of background sounds. Using EEG to measure auditory cortical oscillations, we find that the chance of target detection systematically depends on both power and phase of theta-band (2–6 Hz) but not alpha-band (8–12 Hz) oscillations before target. Detection rates were higher and responses faster when oscillatory power was low and both detection rate and response speed were modulated by phase. Intriguingly, the phase dependency was stronger for miss than for hit trials, suggesting that phase has a inhibiting but not ensuring role for detection. Entrainment of theta range oscillations prominently occurs during the processing of attended complex stimuli, such as vocalizations and speech. Our results demonstrate that this entrainment to attended sensory environments may have negative effects on the detection of individual tokens within the environment, and they support the notion that specific phase ranges of cortical oscillations act as gatekeepers for perception.

Biokatalysatoren — gleichgultig, ob in Form von Enzymen, Prokaryoten oder Eukaryoten — haben sich als wesentlich spezifischer und damit wirkungsvoller als irgendein anorganischer Katalysator erwiesen. Wegen ihres begrenzten Temperatureinsatzbereiches — fur die meisten von ihnen wirken Temperaturen uber 50 °C bereits deaktivierend — und weil sie in der Regel nur in verdunnten wassrigen Systemen agieren, busen sie aber einen grosen Teil dieses Vorteils wieder ein. Hohe Kosten (fur Enzyme) bzw. geringe Wachstumsgeschwindigkeiten (bei Prokaryoten und insbesondere Eukaryoten) tun ein Ubriges.

While a number of studies have measured or determined the images that potential visitors have of tourist destinations (Crompton 1979; Embacher and Buttle 1989; Gartner 1989; Gartner and Hunt 1987; Gartner and Shen 1992; Goodrich 1978; Hunt 1975; Reilly 1990), few have looked at the tourism image that local residents have of the destination area. It might be expected that the image that the host population has of its home area would be important because of its relationship to two aspects of tourism development: (1) it may influence political support for efforts to promote and develop tourism, and (2) it may influence the organic image developed in potential visitors via the information provided by host residents to friends, relatives, and business associates.

At present, there exist a number of on-demand single photon sources with high emission rates and stability even at room temperature. However, their emission wavelength is restricted to specific transitions in single quantum emitters. Single photon generation in the near infrared, possibly within the telecom band, though most urgently needed, is particularly crucial. In this paper, we suggest an experimental method to convert visible single photons from a defect center in diamond to the near infrared. The conversion relies on efficient absorption by colloidal quantum dots and subsequent Stokes-shifted emission. The desired target wavelength can be chosen almost arbitrarily by selecting quantum dots with a suitable emission spectrum. A hollow core photonic crystal fiber selectively filled with a solution of quantum dots was used to achieve at the same time a single photon absorption probability of near unity and a very high re-collection efficiency of Stokes-shifted fluorescence (theoretically estimated to be 26%). A total conversion efficiency of light of 0.1% is achieved. Experimental strategies to significantly enhance this number are presented.