Self-Driving Laboratories for Chemistry and Materials Science.

Self-driving laboratories (SDLs) promise an accelerated application of the scientific method. Through the automation of experimental workflows, along with autonomous experimental planning, SDLs hold the potential to greatly accelerate research in chemistry and materials discovery. This review provides an in-depth analysis of the state-of-the-art in SDL technology, its applications across various scientific disciplines, and the potential implications for research and industry. This review additionally provides an overview of the enabling technologies for SDLs, including their hardware, software, and integration with laboratory infrastructure. Most importantly, this review explores the diverse range of scientific domains where SDLs have made significant contributions, from drug discovery and materials science to genomics and chemistry. We provide a comprehensive review of existing real-world examples of SDLs, their different levels of automation, and the challenges and limitations associated with each domain.

Stress hyperglycaemia following trauma - a survival benefit or an outcome detriment?

PURPOSE OF REVIEW: Stress hyperglycaemia occur often in critically injured patients. To gain new consideration about it, this review compile current as well as known immunological and biochemical findings about causes and emergence. RECENT FINDINGS: Glucose is the preferred energy substrate for fending immune cells, reparative tissue and the cardiovascular system following trauma. To fulfil these energy needs, the liver is metabolically reprogrammed to rebuild glucose from lactate and glucogenic amino acids (hepatic insulin resistance) at the expenses of muscles mass and - to a less extent - fat tissue (proteolysis, lipolysis, peripheral insulin resistance). This inevitably leads to stress hyperglycaemia, which is evolutionary preserved and seems to be an essential and beneficial survival response. It is initiated by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), intensified by immune cells itself and mainly ruled by tumour necrosis factor (TNF)α and catecholamines with lactate and hypoxia inducible factor (HIF)-1α as intracellular signals and lactate as an energy shuttle. Important biochemical mechanisms involved in this response are the Warburg effect as an efficient metabolic shortcut and the extended Cori cycle. SUMMARY: Stress hyperglycaemia is beneficial in an acute life-threatening situation, but further research is necessary, to prevent trauma patients from the detrimental effects of persisting hyperglycaemia.

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis.

Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant interest over the last decades. Concurrent to this development, machine learning (ML) has been increasingly applied in the chemical domain to efficiently uncover hidden patterns in data and accelerate scientific discovery. While the uptake of ML in organocatalysis has been comparably slow, the last two decades have showed an increased interest from the community. This review gives an overview of the work in the field of ML in organocatalysis. The review starts by giving a short primer on ML for experimental chemists, before discussing its application for predicting the selectivity of organocatalytic transformations. Subsequently, we review ML employed for privileged catalysts, before focusing on its application for catalyst and reaction design. Concluding, we give our view on current challenges and future directions for this field, drawing inspiration from the application of ML to other scientific domains.

Active Site Descriptors from 95Mo NMR Signatures of Silica-Supported Mo-Based Olefin Metathesis Catalysts.

The olefin metathesis activity of silica-supported molybdenum oxides depends strongly on metal loading and preparation conditions, indicating that the nature and/or amounts of the active sites vary across compositionally similar catalysts. This is illustrated by comparing Mo-based (pre)catalysts prepared by impregnation (2.5-15.6 wt % Mo) and a model material (2.3 wt % Mo) synthesized via surface organometallic chemistry (SOMC). Analyses of FTIR, UV-vis, and Mo K-edge X-ray absorption spectra show that these (pre)catalysts are composed predominantly of similar isolated Mo dioxo sites. However, they exhibit different reaction properties in both liquid and gas-phase olefin metathesis with the SOMC-derived catalyst outperforming a classical catalyst of a similar Mo loading by ×1.5-2.0. Notably, solid-state 95Mo NMR analyses leveraging state-of-the-art high-field (28.2 T) measurement conditions resolve four distinct surface Mo dioxo sites with distributions that depend on the (pre)catalyst preparation methods. The intensity of a specific deshielded 95Mo NMR signal, which is most prominent in the SOMC-derived catalyst, is linked to reducibility and catalytic activity. First-principles calculations show that 95Mo NMR parameters directly manifest the local strain and coordination environment: acute (SiO-Mo(O)2-OSi) angles and low coordination numbers at Mo lead to highly deshielded 95Mo chemical shifts and small quadrupolar coupling constants, respectively. Natural chemical shift analyses relate the 95Mo NMR signature of strained species to low LUMO energies, which is consistent with their high reducibility and corresponding reactivity. The 95Mo chemical shifts of supported Mo dioxo sites are thus linked to their specific electronic structures, providing a powerful descriptor for their propensity toward reduction and formation of active sites.

Pharmacokinetics and Antifungal Activity of Echinocandins in Ascites Fluid of Critically Ill Patients.

The pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis. The antifungal activity of the echinocandins in ascites fluid was assessed by incubation of Candida albicans and Candida glabrata at concentrations of 0.03 to 16.00 µg/ml. In addition, ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with echinocandins to restore the original concentrations because echinocandins had been lost during sterile filtration. In ascites fluid specimens of 29 patients, echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of echinocandin concentrations in ascites fluid than in plasma. Proliferation of C. albicans in ascites fluid was slower than in culture medium and growth of C. glabrata was lacking, even in the absence of antifungals. In CAS-spiked ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG had no relevant effect. In ascites fluid of our study patients, echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of C. albicans or C. glabrata. Thus, therapeutic doses of AFG, MFG, or CAS may result in ascites fluid concentrations preventing relevant proliferation of C. albicans and C. glabrata, but do not warrant reliable eradication.

Validation of the revised 2018 AAST-OIS classification and the CT severity index for prediction of operative management and survival in patients with blunt spleen and liver injuries.

OBJECTIVES: Non-operative management (NOM) is increasingly utilised in blunt abdominal trauma. The 1994 American Association of Surgery of Trauma grading (1994-AAST) is applied for clinical decision-making in many institutions. Recently, classifications incorporating contrast extravasation such as the CT severity index (CTSI) and 2018 update of the liver and spleen AAST were proposed to predict outcome and guide treatment, but validation is pending. METHODS: CT images of patients admitted 2000-2016 with blunt splenic and hepatic injury were systematically re-evaluated for 1994/2018-AAST and CTSI grading. Diagnostic accuracy, diagnostic odds ratio (DOR), and positive and negative predictive values were calculated for prediction of in-hospital mortality. Correlation with treatment strategy was assessed by Cramer V statistics. RESULTS: Seven hundred and three patients were analysed, 271 with splenic, 352 with hepatic and 80 with hepatosplenic injury. Primary NOM was applied in 83% of patients; mortality was 4.8%. Comparing prediction of mortality in mild and severe splenic injuries, the CTSI (3.1% vs. 10.3%; diagnostic accuracy = 75.4%; DOR = 3.66; p = 0.006) and 1994-AAST (3.3% vs. 10.5%; diagnostic accuracy = 77.9%; DOR = 3.45; p = 0.010) were more accurate compared with the 2018-AAST (3.4% vs. 8%; diagnostic accuracy = 68.2%; DOR = 2.50; p = 0.059). In hepatic injuries, the CTSI was superior to both AAST classifications in terms of diagnostic accuracy (88.7% vs. 77.1% and 77.3%, respectively). CTSI and 2018-AAST correlated better with the need for surgery in severe vs. mild hepatic (Cramer V = 0.464 and 0.498) and splenic injuries (Cramer V = 0.273 and 0.293) compared with 1994-AAST (Cramer V = 0.389 and 0.255; all p < 0.001). CONCLUSIONS: The 2018-AAST and CTSI are superior to the 1994-AAST in correlation with operative treatment in splenic and hepatic trauma. The CTSI outperforms the 2018-AAST in mortality prediction. KEY POINTS: • Non-operative management of blunt abdominal trauma is increasingly applied and correct patient stratification is crucial. • CT-based scoring systems are used to assess injury severity and guide clinical decision-making, whereby the 1994 version of the American Association of Surgery of Trauma Organ Injury Scale (AAST-OIS) is currently most commonly utilised. • Including contrast media extravasation in CT-based grading improves management and outcome prediction. While the 2018-AAST classification and the CT-severity-index (CTSI) better correlate with need for surgery compared to the 1994-AAST, the CTSI is superior in outcome-prediction to the 2018-AAST.

Androgen receptor gene polymorphism and sexual function in midlife women.

PURPOSE: To assess the impact of serum androgen levels and androgen receptor CAG polymorphism on sexual function in 45 healthy midlife women living in a heterosexual relationship. METHODS: Cross-sectional study [Cantonal Ethics Committee Bern (Ref.-Nr. KEK-BE: 087/13)]. MAIN OUTCOME MEASURES: Association between androgen serum levels, androgen receptor CAG polymorphism and sexual function was assessed by the FSFI-d questionnaire. RESULTS: In our cohort of healthy, midlife, well-educated, middle-class, mostly postmenopausal women living in a heterosexual satisfying partnership, sexual function was perceived to remain stable or to decline during menopausal transition with sexual desire scoring lowest (FSFI-d 3.3 ± 0.9). Androgen serum levels did not correlate with sexual function. Mean CAG repeat number was 21.6 ± 1.9. There was a highly inverse though non-significant correlation between female sexual function and AR CAG repeat polymorphism with specifically higher numbers of CAG repeats being significantly positively correlated to more frequent or more severe pain during or after sexual intercourse. CONCLUSION: The AR polymorphism is a non-negligible factor in female sexual function. Future studies on female sexual (dys)function should incorporate its assessment.

Blood glucose concentrations in prehospital trauma patients with traumatic shock: A retrospective analysis.

BACKGROUND: Deranged glucose metabolism after moderate to severe trauma with either high or low concentrations of blood glucose is associated with poorer outcome. Data on prehospital blood glucose concentrations and trauma are scarce. OBJECTIVES: The primary aim was to describe the relationship between traumatic shock and prehospital blood glucose concentrations. The secondary aim was to determine the additional predictive value of prehospital blood glucose concentration for traumatic shock when compared with vital parameters alone. DESIGN: Retrospective analysis of the predefined, observational database of a nationwide Helicopter Emergency Medical Service (34 bases). SETTING: Emergency trauma patients treated by Helicopter Emergency Medical Service between 2005 and 2013 were investigated. PATIENTS: All adult trauma patients (≥18 years) with recorded blood glucose concentrations were enrolled. OUTCOMES: Primary outcome: upper and lower thresholds of blood glucose concentration more commonly associated with traumatic shock. Secondary outcome: additional predictive value of prehospital blood glucose concentrations when compared with vital parameters alone. RESULTS: Of 51 936 trauma patients, 20 177 were included. In total, 220 (1.1%) patients died on scene. Hypoglycaemia (blood glucose concentration 2.8 mmol l or less) was observed in 132 (0.7%) patients, hyperglycaemia (blood glucose concentration exceeding 15 mmol l) was observed in 265 patients (1.3%). Blood glucose concentrations more than 10 mmol l (n = 1308 (6.5%)) and 2.8 mmol l or less were more common in patients with traumatic shock (P < 0.0001). The Youden index for traumatic shock ((sensitivity + specificity) - 1) was highest when blood glucose concentration was 3.35 mmol l (P < 0.001) for patients with low blood glucose concentrations and 7.75 mmol l (P < 0.001) for those with high blood glucose concentrations. In logistic regression analysis of patients with spontaneous circulation on scene, prehospital blood glucose concentrations (together with common vital parameters: Glasgow Coma Scale, heart rate, blood pressure, breathing frequency) significantly improved the prediction of traumatic shock in comparison with prediction by common vital parameters alone (P < 0.0001). CONCLUSION: In adult trauma patients, low and high blood glucose concentrations were more common in patients with traumatic shock. Prehospital blood glucose concentration measurements in addition to common vital parameters may help identify patients at risk of traumatic shock.

Gender-specific homophily on Instagram and implications on information spread.

More and more social interactions happen online. On online social networks such as Instagram, millions of users share, like, and comment on photos and videos every day, interacting with other users world wide, at large scale and at a high rate. These networks do not only introduce new user experiences, but they also enable new insights into human behavior. Here, we use these new possibilities to study homophilic behavior-the tendency of individuals to bond with people similar to themselves. While homophilic behavior has been observed in many contexts, little is known about gender-specific differences and the extent of homophilic behavior of female and male users in online social networks. Based on a unique and extensive data set, covering over 800,000 (directed) Instagram interactions and a time span of three years, we shed light on differences between genders and uncover an intriguing asymmetry of homophily. In particular, we show that female users exhibit homophily to a larger extent than male users. The magnitude of this asymmetry depends on the type of interaction, as differences are more pronounced for 'comment'-interactions than for 'like'-interactions. Given these empirical observations, we further study the implications of such gender differences on the spread of information in social networks in a basic model. We find that on average, a piece of information that originates from a female group reaches significantly more female users than male users.

Intervertebral disc deformation in the lower lumbar spine during object lifting measured in vivo using indwelling bone pins.

Object lifting is often categorized into squat and stoop techniques, with the former believed to protect the back by maintaining a neutral spine, and the latter considered harmful due to spinal flexion. Despite the widespread promotion of these beliefs, there is no evidence to support such dichotomy, as spinal flexion is not conclusively linked to low back pain. This study aimed to investigate intervertebral disc deformation in the lower lumbar spine during squat and stoop lifting using indwelling bone pins. Five healthy males underwent insertion of Kirschner wires into the L3, L4, and L5 spinous processes, followed by biomechanical data collection using magnetic and optical tracking systems during upright standing, isolated flexion/extension, and object lifting with both squat and stoop techniques. Except for one subject, stoop lifting resulted in up to 90 % greater disc wedging compared to squat lifting, with a significant difference at L4/L5 (p = 0.042). The anterior annulus fibrosus experienced 10 % to 40 % more compression during stoop lifting, but no significant differences were found in posterior annulus fibrosus expansion between techniques. Lever arms were about 35 % longer during stoop compared to squat lifting. These results indicate that even though stoop lifting generally led to greater disc deformation, significant deformation was also observed during squat lifting, challenging the notion of maintaining a neutral spine with this technique. Moreover, the considerable variability observed among participants raises concerns about the suitability of current one-size-fits-all lifting guidelines.

Conventional video recordings dependably quantify whole-body lifting strategy using the Stoop-Squat-Index: A methods comparison against motion capture and a reliability study.

Whole-body lifting strategies could be derived from conventional video recordings using the Stoop-Squat-Index, which quantifies the ratio between trunk forward lean and lower extremity joint flexion from 0 (full squat) to 100 (full stoop). The purpose of this study was to compare Stoop-Squat-Indices derived from conventional video recordings to those from a three-dimensional marker-based motion capture system and to evaluate interrater and intrarater reliability of the video-based approach. Thirty healthy participants lifted a 5-kg box under different conditions (freestyle, squat, stoop). Kinematic data were recorded using a Vicon motion capture system (serving as reference standard) and an iPad camera. Stoop-Squat-Indices over the entire lifting cycle were derived separately from both approaches. Agreement was assessed using mean differences (video minus motion capture) and limits of agreement. Reliability was investigated by calculating intraclass correlation coefficients (ICC) and minimal detectable changes (MDC) over the course of the lifting cycle. Systematic errors were identified with Statistical Parametric Mapping-based T-tests. Systematic errors between the video-based and the motion capture-based approach were observed among all conditions. Mean differences in Stoop-Squat-Indices over the lifting cycle ranged from -6.9 to 3.2 (freestyle), from -1.8 to 5.3 (squat) and from -2.8 to -1.1 (stoop). Limits of agreement were lower when the box was close to the floor, and higher towards upright standing. Reliability of the video-based approach was excellent for most of the lifting cycle, with ICC above 0.995 and MDC below 3.5. These findings support using a video-based assessment of Stoop-Squat-Indices to quantify whole-body lifting strategy in field.

Associations between pain-related fear and lumbar movement variability during activities of daily living in patients with chronic low back pain and healthy controls.

Low back pain (LBP) is a global issue involving biological, psychological, and social factors. Pain-related fear has been shown to influence movement behavior, however, its association with some measures of movement behavior, such as spinal movement variability, remains inconclusive. To further investigate this, spinal kinematics during various activities of daily living (i.e., walking, running, lifting, and stair climbing) of 49 patients with chronic LBP and a group of 51 sex-, age-, and BMI-matched healthy controls were used to calculate lumbar spine movement variability which was quantified using different indices (i.e., coefficient of variation, coupling angle variability in vector coding, deviation phase of the continuous relative phase and an angle-angular velocity variability). General and task-specific pain-related fear was assessed using the Tampa Scale of Kinesiophobia and the Photograph Series of Daily Activities-Short Electronic Version, respectively. Linear regression analyses showed no significant association between movement variability and pain-related fear, however, the sample consisted of younger individuals with moderate disability and with low levels of pain and pain-related fear. In addition, the different variability indices were weakly correlated and varied greatly depending on the method used and the task performed. Therefore, comparisons between studies with different movement variability calculation methods or different activities should be treated with caution.

Predicted vs. measured paraspinal muscle activity in adolescent idiopathic scoliosis patients: EMG validation of optimization-based musculoskeletal simulations.

Musculoskeletal (MSK) models offer great potential for predicting the muscle forces required to inform more detailed simulations of vertebral endplate loading in adolescent idiopathic scoliosis (AIS). In this work, simulations based on static optimization were compared with in vivo measurements in two AIS patients to determine whether computational approaches alone are sufficient for accurate prediction of paraspinal muscle activity during functional activities. We used biplanar radiographs and marker-based motion capture, ground reaction force, and electromyography (EMG) data from two patients with mild and moderate thoracolumbar AIS (Cobb angles: 21° and 45°, respectively) during standing while holding two weights in front (reference position), walking, running, and object lifting. Using a fully automated approach, 3D spinal shape was extracted from the radiographs. Geometrically personalized OpenSim-based MSK models were created by deforming the spine of pre-scaled full-body models of children/adolescents. Simulations were performed using an experimentally controlled backward approach. Differences between model predictions and EMG measurements of paraspinal muscle activity (both expressed as a percentage of the reference position values) at three different locations around the scoliotic main curve were quantified by root mean square error (RMSE) and cross-correlation (XCorr). Predicted and measured muscle activity correlated best for mild AIS during object lifting (XCorr's ≥ 0.97), with relatively low RMSE values. For moderate AIS as well as the walking and running activities, agreement was lower, with XCorr reaching values of 0.51 and comparably high RMSE values. This study demonstrates that static optimization alone seems not appropriate for predicting muscle activity in AIS patients, particularly in those with more than mild deformations as well as when performing upright activities such as walking and running.

Utility of PCR in diagnosis of invasive fungal infections: real-life data from a multicenter study.

Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the "gold standard." In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests.

The relationship between different body mass index categories and chair rise performance in adult women.

An important prerequisite to carry out daily activities is the sit-to-stand movement. However, in obese people, this movement is characterized by altered biomechanics, which might lead to daily life activity impairments. The aim of this study was to investigate whether there are differences in kinetic and kinematic variables between three different BMI categories when performing a specific sit-to-stand test. Thirty-six adult women (BMI = 17-45 kg/m²) performed the sit-to stand test five times consecutively and as quickly as possible. Analyses of variance were used to determine differences between three BMI groups (normal or overweight: BMI < 30 kg/m²; obese: 30 ≤ BMI < 35; severely obese: BMI ≥ 35). Peak and mean vertical sacrum velocity indicated a decrease in severely obese subjects. Obese and severely obese individuals did not show higher fatigue over the five consecutive movements. Peak force and rate of force development decreased in normal or overweight subjects. The ability to successfully complete the test decreased with a higher BMI, probably due to a reduced ability to rapidly generate a high force.

Biomechanical factors associated with non-specific low back pain in adults: A systematic review.

Low back pain (LBP) can result in increased direct medical and non-medical costs to patients, employers, and health care providers. This systematic review aimed to provide a better understanding of the biomechanical factors associated with chronic non-specific LBP in adults. SCOPUS, ScienceDirect, MEDLINE, and Web of Science databases were searched. In total, 26 studies were included and significant differences were noted between healthy controls and LBP patients in various motion. Biomechanical factors among adults with non-specific LBP were altered and differed as compared to healthy controls in various motion might be to compensate the pain during those motions. This review highlighted the biomechanical differences across those with non-specific LBP and healthy adults. Both groups showed a similar level of pain during functional tasks but LBP patients suffered from a moderate level of disability. Future studies should not rely on questionnaire-based pain scale only. The biomechanical factors summarized in this review can be used to diagnose non-specific LBP accurately, and as modifiable targets for exercise-based intervention.

Candida auris in Austria-What Is New and What Is Different.

Candida auris is a novel and emerging pathogenic yeast which represents a serious global health threat. Since its first description in Japan 2009, it has been associated with large hospital outbreaks all over the world and is often resistant to more than one antifungal drug class. To date, five C. auris isolates have been detected in Austria. Morphological characterization and antifungal susceptibility profiles against echinocandins, azoles, polyenes and pyrimidines, as well as the new antifungals ibrexafungerp and manogepix, were determined. In order to assess pathogenicity of these isolates, an infection model in Galleria mellonella was performed and whole genome sequencing (WGS) analysis was conducted to determine the phylogeographic origin. We could characterize four isolates as South Asian clade I and one isolate as African clade III. All of them had elevated minimal inhibitory concentrations to at least two different antifungal classes. The new antifungal manogepix showed high in vitro efficacy against all five C. auris isolates. One isolate, belonging to the African clade III, showed an aggregating phenotype, while the other isolates belonging to South Asian clade I were non-aggregating. In the Galleria mellonella infection model, the isolate belonging to African clade III exhibited the lowest in vivo pathogenicity. As the occurrence of C. auris increases globally, it is important to raise awareness to prevent transmission and hospital outbreaks.

Catabolism highly influences ICU-acquired hypernatremia in a mainly trauma and surgical cohort.

PURPOSE: To further analyse causes and effects of ICU-acquired hypernatremia. METHODS: This retrospective, single-centre study, analysed 994 patients regarding ICU-acquired hypernatremia. Non-hypernatremic patients (n = 617) were compared to early-hypernatremic (only before ICU-day 4; n = 87), prolonged-hypernatremic (before and after ICU-day 4; n = 169) and late-hypernatremic patients (only after ICU-day 4; n = 121). Trends in glomerular filtration rate (eGFR), urea-to-creatinine ratio (UCR), fraction of urea in total urine osmolality and urine sodium were compared. Risk factors for i) the development of hypernatremia and ii) mortality were determined. RESULTS: Thirty-eight percent (n = 377) developed ICU-acquired hypernatremia. Specifically in the prolonged- and late-group, decreased eGFRs and urine sodium but increased UCR and fractions of urea in urine osmolality were present. Decreased eGFR was a risk factor for the development of hypernatremia in all groups; disease severity and increased catabolism particularly in the prolonged- and late-hypernatremic group. Increased age, SAPS-III and signs of catabolism but not the development of hypernatremia itself was identified as significant risk factor for mortality. CONCLUSIONS: Late- and prolonged-hypernatremia is highly related to an increased protein metabolism. Besides excessive catabolism, initial disease severity and a decrease in renal function must be considered when confronted with ICU-acquired hypernatremia.

Extractive electrospray ionization mass spectrometry-enhanced sensitivity using an ion funnel.

Electrodynamic ion funnel interfaces for electrospray ionization (ESI) have shown to enhance the sensitivity of measurements by more than 2 orders of magnitude in the intermediate pressure region of the instrument (1-30 Torr). In this study, we use an ion funnel at ambient pressure to enhance the sensitivity of extractive electrospray ionization (EESI) by spraying directly into the ion funnel. EESI is a powerful ionization technique that is capable of handling complex matrixes that may contain dozens of compounds. Our results using atenolol, salbutamol, and cocaine as test compounds show that we can improve the limit of detection for these compounds by more than 3 orders of magnitude compared to standard EESI experiments.