Development of new binary expression systems for plant synthetic biology.

KEY MESSAGE: A novel plant binary expression system was developed from the compactin biosynthetic pathway 27 of Penicillium citrinum ML-236B. The system achieved >fivefold activation of gene expression in 28 transgenic tobacco. A diverse and well-characterized genetic toolset is fundamental to achieve the overall goals of plant synthetic biology. To properly coordinate expression of a multigene pathway, this toolset should include binary systems that control gene expression at the level of transcription. In plants, few highly functional, orthogonal transcriptional regulators have been identified. Here, we describe the process of developing synthetic plant transcription factors using regulatory elements from the Penicillium citrinum ML-236B (compactin) pathway. This pathway contains several genes including mlcA and mlcC that are transcriptionally regulated in a dose-dependent manner by the activator mlcR. In Nicotiana benthamiana, we first expressed mlcR with several cognate synthetic promoters driving expression of GFP. Synthetic promoters contained operator sequences from the compactin gene cluster. Following identification of the most active synthetic promoter, the DNA-binding domain from mlcR was used to generate chimeric transcription factors containing variable activation domains, including QF from the Neurospora crassa Q-system. Activity was measured at both protein and RNA levels which correlated with an R2 value of 0.94. A synthetic transcription factor with a QF activation domain increased gene expression from its synthetic promoter up to sixfold in N. benthamiana. Two systems were characterized in transgenic tobacco plants. The QF-based plants maintained high expression in tobacco, increasing expression from the cognate synthetic promoter by fivefold. Transgenic plants and non-transgenic plants were morphologically indistinguishable. The framework of this study can easily be adopted for other putative transcription factors to continue improvement of the plant synthetic biology toolbox.

Multichannel laser diode to polymer waveguide array coupling with a double-aspheric lens.

An optical system for multichannel coupling of laser arrays to polymer waveguide array probes with a single biconvex lens is developed. The developed cylindrical module with 13 mm and 20 mm in diameter and length, respectively, enables coupling of eight individual optical channels using an aspheric lens. Specific coupling with crosstalk below -13d B for each channel and quasi-uniform coupling over all channels is achieved for a waveguide array with 100 µm lateral facet pitch at the incoupling site. The polymer waveguide technology allows for tapering of the lateral waveguide pitch to 25 µm toward the tip of the flexible waveguide array. SU-8 and PMMA are used as the waveguide core and cladding, respectively. The optical coupling module is designed as a prototype for preclinical evaluation of optical neural stimulators.

The formation of Charon's red poles from seasonally cold-trapped volatiles.

A unique feature of Pluto's large satellite Charon is its dark red northern polar cap. Similar colours on Pluto's surface have been attributed to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon's high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.

Coexistence of antithrombin deficiency and suspected inferior vena cava atresia in an adolescent and his mother - case report and clinical implications.

BACKGROUND: Antithrombin deficiency (ATD) is an autosomal dominant thrombophilia presenting with varying phenotypes. In pediatric patients with ATD, thrombosis typically develops during the neonatal period or adolescence. However, to date there are no consistent recommendations on the therapeutic management of children with ATD. Inferior vena cava atresia (IVCA) belongs to a range of congenital or acquired vena cava malformations and is described as an independent risk factor for thrombosis. The present case report explores two cases of combined ATD and IVCA in an adolescent and his mother. CASE PRESENTATION: A 14-year-old male presented with extensive deep venous thromboses (DVTs) of both lower extremities as well as an IVCA. The patient had previously been diagnosed with an asymptomatic ATD without therapeutic consequences at that time. His mother was suffering from an ATD and had herself just been diagnosed with IVCA, too. The DVTs in the adolescent were treated by systemic anticoagulation and catheter-directed local thrombolysis causing favourable results. Yet, despite adequate oral anticoagulation the DVTs in both lower extremities reoccurred within 1 week after the patient was discharged from hospital. This time, thrombolysis could not be fully achieved. Surprisingly, probing and stenting of the IVCA was achieved, indicating an acquired IVCA which could have occurred after undetected thrombosis in early childhood. Genetic analyses showed the same mutation causing ATD in both son and mother: heterozygote missense mutation c.248 T > C, p.(Leu83Pro), within the heparin binding domain of antithrombin. This mutation was never reported in mutation databases before. CONCLUSIONS: To our knowledge this is the first case report discussing combined ATD and IVCA in two family members. Since ATDs present with clinical heterogeneity, taking a thorough family history is crucial for the anticipation of possible complications in affected children and decisions on targeted diagnostics and therapeutic interventions. Affected families must be educated on risk factors and clinical signs of thrombosis and need an immediate diagnostic workup in case of clinical symptoms. IVCA in patients with ATD could occur due to thrombotic occlusion at a very early age. Therefore, in case of family members with IVCA and ATD ultrasound screening in newborns should be considered.

Translational and reorientational dynamics in deep eutectic solvents.

We performed rheological measurements of the typical deep eutectic solvents (DESs) glyceline, ethaline, and reline in a very broad temperature and dynamic range, extending from the low-viscosity to the high-viscosity supercooled-liquid regime. We find that the mechanical compliance spectra can be well described by the random free-energy barrier hopping model, while the dielectric spectra on the same materials involve significant contributions arising from reorientational dynamics. The temperature-dependent viscosity and structural relaxation time, revealing non-Arrhenius behavior typical for glassy freezing, are compared to the ionic dc conductivity and relaxation times determined by broadband dielectric spectroscopy. For glyceline and ethaline, we find essentially identical temperature dependences for all dynamic quantities. These findings point to a close coupling of the ionic and molecular translational and reorientational motions in these systems. However, for reline, the ionic charge transport appears decoupled from the structural and reorientational dynamics, following a fractional Walden rule. In particular, at low temperatures, the ionic conductivity in this DES is enhanced by about one decade compared to expectations based on the temperature dependence of the viscosity. The results for all three DESs can be understood without invoking a revolving-door mechanism previously considered as a possible charge-transport mechanism in DESs.

Perioperative echocardiography-guided hemodynamic therapy in high-risk patients: a practical expert approach of hemodynamically focused echocardiography.

The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO2) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO2. The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy.

[New aspects of rapid sequence induction including treatment of pulmonary aspiration]. / Neue Aspekte der "rapid sequence induction" einschließlich Behandlung der pulmonalen Aspiration.

Pulmonary aspiration of solid components leads to displacement of the tracheobronchial tree, the aspiration of acidic gastric juices to chemical pneumonitis (Mendelson's syndrome) and the aspiration of oropharyngeal secretions or gastrointestinal pathogens to aspiration pneumonia. Principally, pulmonary aspiration can occur at any stage of anesthesia. In the clinical routine the aim must therefore be to identify those patients who have an increased risk of aspiration. When this is successful, measures can be taken to reduce the risk; these can be regional anaesthesia or the performance of general anaesthesia as rapid sequence induction (RSI). If severe pulmonary aspiration occurs despite all preventive measures, mostly during induction of anaesthesia, extensive experience and rapid action are necessary. This can only be achieved if the induction to RSI is performed by three persons with supervision of the trainee anaesthetist by a consultant anaesthetist.

[Implementation of emergency classifications-Where do we stand? : Results of a nationwide survey]. / Der Umgang mit Notfallklassifikationen ­ Wo stehen wir? : Ergebnisse einer deutschlandweiten Umfrage.

BACKGROUND: This study aimed to determine the current state of implementation of the recommendations for the classification of emergency surgery published in 2016 by the German societies of anesthesiology (BDA/DGAI), surgery (BDC/DGCH) and operating room management (VOPM). METHODS: Based on these societies' recommendations, various organizational issues were explored using an online questionnaire that was limited to German operating room (OR) managers and coordinators for hospitals that had surgical programs and at least 200 hospital beds. RESULTS: A total of 550 hospitals were contacted and 274 participated in the survey (49.8%). Of these 70.7% reported that they had implemented the recommendations, and 15.2% were aware of the recommendations but did not consistently apply them. Of the participating OR managers and coordinators that had either implemented or were aware of the recommendations, 78.2% agreed that the standardized definition of medical emergencies led to improvements in emergency treatment but 33.6% stated that the defined response intervals for emergency categories induced a certain degree of subjectivity in categorizing emergencies. Additional in-house guidelines specifically for the most frequent surgeries were or would be welcomed by 80.1% of the respondents and 39.1% of the surveyed hospitals had already implemented such guidelines. Of the OR managers and coordinators, 62.9% were informed about their emergency volumes and 47.3% stated that they regularly assessed them. There was no dedicated capacity for emergency care in 65.2% of hospitals. Of the respondents 3.9% stated that a separate emergency OR was reserved with a freely available team, which, during core operating hours, could be used for interdisciplinary emergency care and 26.2% of hospitals considered the capacity required for emergency procedures when planning the OR program or determining OR capacities. CONCLUSION: The recommendations for classifying emergency operations are an essential and generally accepted control mechanism in OR coordination. They simplify interdisciplinary coordination and communication when dynamically incorporating emergency procedures into an OR program. Most OR managers and coordinators view the recommendations as improving the speed of action in emergency care. To support the adoption of emergency classifications within an organization it may be advisable to incorporate them into the OR statutes and integrate them within the hospital information systems. The majority of participants supported additional specifications based on medical indicators for classifying the most frequent emergency operations. Being cognizant of key metrics concerning in-house emergency volume represents a crucial basis for interdisciplinary OR management and emergency care integration. Contrary to common perception, blocking fixed OR capacities remains the exception. When establishing a concept to provide emergency capacity, it is advisable to align developments with demand calculations based on in-house figures and to emphasize interdisciplinary participation and consensus.

[Sepsis-associated encephalopathy : A nationwide survey on diagnostic procedures and neuromonitoring in German intensive care units]. / Sepsis-assoziierte Enzephalopathie : Eine bundesweite Umfrage zu Verfahren der Diagnostik und des Neuromonitorings auf deutschen Intensivstationen.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is one of the most frequent causes of neurocognitive impairment in intensive care patients. It is associated with increased hospital mortality and poor long-term neurocognitive outcome. To date there are no evidence-based recommendations for the diagnostics and neuromonitoring of SAE. OBJECTIVE: The aim of the study was to evaluate the current clinical practice of diagnostics and neuromonitoring of SAE on intensive care units (ICU) in Germany. MATERIAL AND METHODS: Based on available literature focusing on SAE, a questionnaire consisting of 26 items was designed and forwarded to 438 members of the Scientific Working Group for Intensive Care Medicine (WAKI) and the Scientific Working Group for Neuroanesthesia (WAKNA) as an online survey. RESULTS: The total participation rate in the survey was 12.6% (55/438). A standardized diagnostic procedure of SAE was reported by 21.8% (12/55) of the participants. The majority of participants preferred delirium screening tools (50/55; 90.9%) and the clinical examination (49/55; 89.1%) to detect SAE. Brain imaging (26/55; 47.3%), laboratory/biomarker determination (15/55; 27.3%), electrophysiological techniques (14/55; 25.5%) and cerebrospinal fluid examination (12/55; 21.8%) are less frequently performed. The follow-up examination of SAE is most frequently performed by a clinical examination (45/55; 81.8%). Neuromonitoring techniques, such as continuous electroencephalography (31/55; 56.4%), transcranial doppler sonography (31/55; 56.4%) and near-infrared spectroscopy (18/55, 32.7%) are not frequently used. We observed statistically significant differences between the theoretically attributed importance and clinical practice. The great majority of respondents (48/55; 87.3%) endorse the development of guidelines containing recommendations for diagnostics and neuromonitoring in SAE. DISCUSSION: This explorative survey demonstrated a great heterogeneity in diagnostics and neuromonitoring of SAE in German ICUs. Uniform concepts have not yet been established but are desired by the majority of study participants. Innovative biomarkers of neuroaxonal injury in blood and cerebrospinal fluid as well as electrophysiological and brain imaging techniques could provide valuable prognostic information on the neurocognitive outcome of patients and would thus be a useful addition to the clinical assessment of ICU patients with SAE.

[Perioperative optimization using hemodynamically focused echocardiography in high-risk patients-A practice guide]. / Perioperative Optimierung mittels auf die Hämodynamik fokussierter Echokardiographie bei Hochrisikopatienten ­ eine Praxisanleitung.

BACKGROUND: The number of high-risk patients undergoing surgery is steadily increasing. In order to maintain and, if necessary, optimize perioperative hemodynamics as well as the oxygen supply to the organs (DO2) in this patient population, a timely assessment of cardiac function and the underlying pathophysiological causes of hemodynamic instability is essential for the anesthesiologist. A variety of hemodynamic monitoring procedures are available for this purpose; however, due to method-immanent limitations they are often not able to directly identify the underlying cause of cardiovascular impairment. OBJECTIVE: To present a stepwise algorithm for a perioperative echocardiography-based hemodynamic optimization in noncardiac surgery high-risk patients. In this context, echocardiography on demand according to international guidelines can be performed under certain conditions (hemodynamic instability, nonresponse to hemodynamic treatment) as well as in the context of a planned intraoperative procedure, mostly as a transesophageal echocardiography. METHODS AND RESULTS: Hemodynamically focused echocardiography as a rapidly available bedside method, enables the timely diagnosis and assessment of cardiac filling obstructions, volume status and volume response, right and left heart function, and the function of the heart valves. CONCLUSION: Integrating all echocardiographic findings in a differentiated assessment of the patient's cardiovascular function enables a (patho)physiologically oriented and individualized hemodynamic treatment.

Ionic conductivity and relaxation dynamics in plastic crystals with nearly globular molecules.

We have performed a dielectric investigation of the ionic charge transport and the relaxation dynamics in plastic crystalline 1-cyano-adamantane (CNA) and in two mixtures of CNA with the related plastic crystals adamantane or 2-adamantanon. Ionic charge carriers were provided by adding 1% of Li salt. The molecules of these compounds have nearly globular shape and, thus, the so-called revolving-door mechanism assumed to promote ionic charge transport via molecular reorientations in other PC electrolytes should not be active here. Indeed, a comparison of the dc resistivity and the reorientational α-relaxation times in the investigated PCs reveals complete decoupling of both dynamics. Similar to other PCs, we find a significant mixing-induced enhancement of the ionic conductivity. Finally, these solid-state electrolytes reveal a second relaxation process, slower than the α-relaxation, which is related to ionic hopping. Due to the mentioned decoupling, it can be unequivocally detected and is not superimposed by the reorientational contributions as found for most other ionic conductors.

[Perioperative blood pressure management : What is the optimal pressure?] / Perioperatives Blutdruckmanagement : Was ist der optimale Druck?

BACKGROUND: Measurement of blood pressure is part of standard monitoring procedures in anesthesia, in addition to the other vital parameters of heart frequency and peripheral oxygen saturation. In recent years the relevance of the duration and extent of perioperative episodes of hypotension for the occurrence of postoperative complications or even increased mortality have become the focus of scientific investigations. OBJECTIVE: The aim of this review is to briefly recapitulate the physiological aspects of blood pressure and to describe the pathophysiology and risk factors of perioperative hypotension. It describes which potential organ damage can be caused by hypotension and discusses which perioperative blood pressure values are acceptable without harming the patient. METHODS: Review and analysis of the currently available literature. RESULTS: Perioperative hypotension is defined by either absolute systolic arterial pressure (SAP) or mean arterial pressure (MAP) thresholds and by relative blood pressure declines from an individual preoperative baseline value. For the definition of absolute and relative thresholds it needs to be considered that the ultimate target is an adequate perfusion pressure (and not the MAP) and that the preinduction blood pressure is a poor reflection of the patients' normal blood pressure profile. Risk factors for an intraoperative drop in blood pressure are advanced age, higher American Society of Anesthesiologists (ASA) status, low blood pressure prior to induction of anesthesia, the premedication, e.g. angiotensin-converting enzyme (ACE) inhibitors, the anesthesia technique (combination of general and epidural anesthesia) and emergency surgery. The lowest tolerable intraoperative blood pressure should be defined according to the individual patient's preoperative blood pressure and risk profile. Individual thresholds should be determined for the severity and duration of intraoperative hypotension. Empirically, MAP values <65 mm Hg and relative pressure declines of >20-30% are often recommended as thresholds. Below critical blood pressure values the risk of postoperative organ damage (myocardium, kidneys and central nervous system) and mortality increases with longer duration of hypotension. Older people and high-risk patients (e.g. patients in vascular surgery) have a poorer and shorter tolerance of low blood pressure. Postoperative organ complications can be minimized by maintenance of an adequate intraoperative blood pressure CONCLUSION: Anesthesiologists should avoid extensive and prolonged hypotension by timely interventions in order to improve the postoperative outcome of patients.

[Perioperative pharmacological circulatory support in daily clinical routine]. / Perioperative medikamentöse Kreislaufunterstützung in der täglichen Routine.

Perioperative phases of hypotension are associated with an increase in postoperative complications and organ damage. Whereas some years ago hemodynamic stabilization was primarily carried out by volume supplementation, in recent years the use and dosing of cardiovascular-active substances has significantly increased. But like intravascular volume therapy, also substances with a cardiovascular effect have therapeutic margins, and thus, potential side effects. This review article discusses indications for each cardiovascular-active agent, weighing up advantages and disadvantages. Special attention is paid to the question how to administrate them: central venous catheter vs. peripheral indwelling venous cannula. The authors come to the conclusion that it is not a question of whether it is principally allowed to apply cardiovascular-active drugs via peripheral veins but more importantly, what should be taken into consideration if a peripheral venous access is used. This article provides concise recommendations.

[Volumetric capnography for analysis and optimization of ventilation and gas exchange]. / Volumetrische Kapnographie zur Analyse und Optimierung von Ventilation und Gasaustausch.

Capnography as the graphical representation of the expiratory carbon dioxide (CO2) concentration, is an essential component of monitoring of every ventilated patient, in addition to pulse oximetry. Capnography demonstrates the kinetics of CO2 in a noninvasive way and in real time. In the daily routine anesthesia, it mainly serves for identification of the correct intubation and adaptation of the respiratory minute volume to be applied; however, capnography can also provide much more far-reaching and clinically particularly valuable information, especially in the form of volumetric capnography (VCap) that is not yet so widely clinically available. These include monitoring and optimization of ventilation and assessment of gas exchange. This article presents parameters for making decisions at the bedside, which could previously only be obtained by extensive, more invasive, nonautomated procedures.

[Foundations of Volumetric capnography : Principles of monitoring of metabolism and hemodynamics]. / Grundlagen der Volumetrischen Kapnographie : Prinzipien der Überwachung von Stoffwechsel und Hämodynamik.

Capnography is the graphical representation of the carbon dioxide (CO2) concentration in expired air. Using this monitoring procedure, the kinetics of CO2 of mechanically ventilated patients can be assessed in a noninvasive way and in real time. This article highlights the importance, particularly of volumetric capnography (VCap), for clinical monitoring of mechanically ventilated patients. The procedure provides important information on the breathing, ventilation, metabolism and hemodynamics of patients.

International survey of neurosurgical anesthesia (iSonata) : An international survey of current practices in neurosurgical anesthesia.

BACKGROUND: No standardized recommendations have been currently defined for anesthesia management of patients undergoing elective intracranial surgery. It can therefore be assumed that international clinical institutions have diverging approaches or standard operating procedures (SOP) which determine the type of general anesthesia, hemodynamic management, neuromuscular blockade, implementation of hypothermia and postoperative patient care. OBJECTIVE: This international survey aimed to assess perioperative patient management during elective intracranial procedures. This survey was performed from February to October 2018 and 311 neurosurgical, maximum care centers across 19 European countries were contacted. The aim was to evaluate the anesthesia management to provide relevant data of neuroanesthesia practices across European centers. The survey differentiated between vascular and non-vascular as well as supratentorial and infratentorial procedures. RESULTS: A total of 109 (35.0%) completed questionnaires from 15 European countries were analyzed. The results illustrated that total intravenous anesthesia was most commonly implemented during elective intracranial procedures (83.8%). All centers performed endotracheal intubation prior to major intracranial surgery (100%). Central venous lines were placed in 63.3% of cases. Moderate intraoperative hypothermia was carried out in 12.8% of the procedures, especially during vascular supratentorial and infratentorial surgery. A neuromuscular blockade during surgery was implemented in 74.1% of patients. Assessment of the neuromuscular junction was performed in 59.2% of cases, 76.7% of patients were immediately extubated in the operating room. 84.7% of these patients were directly transferred to a monitoring ward or an intensive care unit (ICU) and 55.1% of ventilated patients were transferred directly to an ICU. CONCLUSION: The data demonstrate that many aspects of anesthesia management during elective intracranial surgery vary between European institutions. The data also suggest that a broad consensus exists regarding the implementation of total intravenous anesthesia, airway management (endotracheal intubation), the implementation of urinary catheters, large bore peripheral venous lines and the broad availability of cross-matched red blood cell concentrates. Nevertheless, anesthesia management (e.g. central venous catheterization, moderate hypothermia, neuromuscular monitoring) is still handled differently across many European institutions. A lack of standardized guidelines defining anesthetic management in patients undergoing intracranial procedures could explain this variability. Further studies could help establish optimal anesthesia management for these patients. This in turn could help in the development of national and international guidelines and SOPs which could define optimal management strategies for intracranial procedures.

Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. METHODS: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). RESULTS: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. CONCLUSIONS: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

Odd and even Kondo effects from emergent localization in quantum point contacts.

A quantum point contact (QPC) is a basic nanometre-scale electronic device: a short and narrow transport channel between two electron reservoirs. In clean channels, electron transport is ballistic and the conductance is then quantized as a function of channel width with plateaux at integer multiples of 2e(2)/h (where e is the electron charge and h is Planck's constant). This can be understood in a picture where the electron states are propagating waves, without the need to account for electron-electron interactions. Quantized conductance could thus be the signature of ultimate control over nanoscale electron transport. However, even studies with the cleanest QPCs generically show significant anomalies in the quantized conductance traces, and there is consensus that these result from electron many-body effects. Despite extensive experimental and theoretical studies, understanding these anomalies is an open problem. Here we report that the many-body effects have their origin in one or more spontaneously localized states that emerge from Friedel oscillations in the electron charge density within the QPC channel. These localized states will have electron spins associated with them, and the Kondo effect--related to electron transport through such localized electron spins--contributes to the formation of the many-body state. We present evidence for such localization, with Kondo effects of odd or even character, directly reflecting the parity of the number of localized states; the evidence is obtained from experiments with length-tunable QPCs that show a periodic modulation of the many-body properties with Kondo signatures that alternate between odd and even Kondo effects. Our results are of importance for assessing the role of QPCs in more complex hybrid devices and for proposals for spintronic and quantum information applications. In addition, our results show that tunable QPCs offer a versatile platform for investigating many-body effects in nanoscale systems, with the ability to probe such physics at the level of a single site.

Plastic-crystalline solid-state electrolytes: Ionic conductivity and orientational dynamics in nitrile mixtures.

Many plastic crystals, molecular solids with long-range, center-of-mass crystalline order but dynamic disorder of the molecular orientations, are known to exhibit exceptionally high ionic conductivity. This makes them promising candidates for applications as solid-state electrolytes, e.g., in batteries. Interestingly, it was found that the mixing of two different plastic-crystalline materials can considerably enhance the ionic dc conductivity, an important benchmark quantity for electrochemical applications. An example is the admixture of different nitriles to succinonitrile, the latter being one of the most prominent plastic-crystalline ionic conductors. However, until now, only few such mixtures were studied. In the present work, we investigate succinonitrile mixed with malononitrile, adiponitrile, and pimelonitrile to which 1 mol. % of Li ions was added. Using differential scanning calorimetry and dielectric spectroscopy, we examine the phase behavior and the dipolar and ionic dynamics of these systems. We especially address the mixing-induced enhancement of the ionic conductivity and the coupling of the translational ionic mobility to the molecular reorientational dynamics, probably arising via a "revolving-door" mechanism.

Head-to-head comparison of two continuous glucose monitoring systems on a cardio-surgical ICU.

In critical illness hypo-and hyperglycemia have a negative influence on patient outcome. Continuous glucose monitoring (CGM) could help in early detection of hypo-and hyperglycemia. A requirement for these new methods is an acceptable accuracy and precision in clinical practice. In this pilot study we prospectively evaluated the accuracy and precision of two CGM sensors (subcutaneous sensor: Sentrino®, Medtronic and intravasal sensor: Glucoclear®, Edwards) in 20 patients on a cardio-surgical ICU in a head to head comparison. CGM data were recorded for up to 48 h and values were compared with blood-gas-analysis (BGA) values, analysed with Bland-Altman-plots and color-coded surveillance error-grids. Shown are means ± standard deviations. In total 270/255 intravasal/subcutaneous pairs with BGA-values were analysed. The average runtime of the sensors was 28.4 ± 6.4 h. Correlation with BGA values yielded a correlation coefficient of 0.76 (subcutaneous sensor) and 0.92 (intravasal sensor). The Bland Altman Plots revealed an accuracy of 2.5 mg/dl, and a precision of + 43.0 mg/dl to - 38.0 mg/dl (subcutaneous sensor) and an accuracy of - 6.0 mg/dl, and a precision of + 12.4 mg/dl to - 24.4 mg/dl (intravasal sensor). No severe hypoglycemic event, defined as BG level below 40 mg/dl, occurred during treatment. Both sensors showed good accuracy in comparison to the BGA values, however they differ regarding precision, which in case of the subcutaneous sensor is considerable high.