The role of well-child visits in detecting developmental delay in preschool children.

BACKGROUND: Early detection of developmental delay (DD) in preschool children is crucial for counselling parents, initiating diagnostic work-up, and starting early intervention (EI). METHODS: We conducted a register study of all preschool children referred for EI in the Canton of Zurich, Switzerland, in 2017 (N = 1,785) and used an online survey among primary care physicians (PCPs, N = 271) to evaluate the care service of DD children. RESULTS: PCPs accounted for 79.5% of all referrals by physicians and had correctly referred over 90% of the children in need of EI at an average age of 39.3 months (SD 8.9). In the survey, which represents 59.2% of all pediatricians and 11.3% of all general practitioners in the Canton, PCPs reported performing a mean of 13.5 (range 0-50, SD 10.7) well-child visits per week to preschool children and estimated well-child visits to be the most frequent type of consultation (66.7%) for the identification of DD. Parents' hesitancy in accepting further evaluation or support were reported by 88.7%. CONCLUSIONS: Most preschool children with DD are identified in well-child visits. These visits represent an ideal opportunity for early detection of developmental impairment and initiation of EI. Carefully addressing parents' reservations could reduce the rate of refusal, thus improving early support for children with DD.

The association between lumbar paraspinal muscle functional cross-sectional area on MRI and regional volumetric bone mineral density measured by quantitative computed tomography.

Osteosarcopenia is a common condition among elderly and postmenopausal female patients. Site-specific bone mineral density is more predictive of bone-related complications. Few studies have investigated muscle-bone associations. Our results demonstrated that in women, significant positive associations between paraspinal muscles FCSA and vBMD exist at different lumbosacral levels. These regional differences should be considered when interpreting bone-muscle associations in the lumbar spine. INTRODUCTION: There is increasing evidence between bone and muscle volume associations. Previous studies have demonstrated comorbidity between osteoporosis and sarcopenia. Recent studies showed that sarcopenic subjects had a fourfold higher risk of concomitant osteoporosis compared to non-sarcopenic individuals. Although site-specific bone mineral density (BMD) assessments were reported to be more predictive of bone-related complications after spinal fusions than BMD assessments in general, there are few studies that have investigated level-specific bone-muscle interactions. The aim of this study is to investigate the associations between muscle functional cross-sectional area (FCSA) on magnetic resonance imaging (MRI) and site-specific quantitative computed tomography (QCT) volumetric bone mineral density (vBMD) in the lumbosacral region among spine surgery patients. METHODS: We retrospectively reviewed a prospective institutional database of posterior lumbar fusion patients. Patients with available MRI undergoing posterior lumbar fusion were included. Muscle measurements and FCSA were conducted and calculated utilizing a manual segmentation and custom-written program at the superior endplate of the L3-L5 vertebrae level. vBMD measurements were performed and calculated utilizing a QCT pro software at L1-L2 levels and bilateral sacral ala. We stratified by sex for all analyses. RESULTS: A total of 105 patients (mean age 61.5 years and 52.4% females) were included. We found that female patients had statistically significant lower muscle FCSA than male patients. After adjusting for age and body mass index (BMI), there were statistically significant positive associations between L1-L2 and S1 vBMD with L3 psoas FCSA as well as sacral ala vBMD with L3 posterior paraspinal and L5 psoas FCSA. These associations were not found in males. CONCLUSIONS: Our results demonstrated that in women, significant positive associations between the psoas and posterior paraspinal muscle FCSA and vBMD exist in different lumbosacral levels, which are independent of age and BMI. These regional differences should be considered when interpreting bone and muscle associations in the lumbar spine.

Dysphagia incidence in intensive care unit patients with coronavirus disease 2019: retrospective analysis following systematic dysphagia screening.

OBJECTIVE: Post-extubation dysphagia in critically ill patients is known to affect about 18 per cent of mixed medical-surgical intensive care unit patients. This study investigated the incidence of post-extubation dysphagia in adult intensive care unit patients with coronavirus disease 2019. METHOD: This study was a retrospective analysis of consecutive intensive care unit patients prospectively screened for dysphagia. Systematic screening of all extubated intensive care unit patients at our tertiary centre was performed using the Bernese intensive care unit dysphagia algorithm. The primary outcome measure was the incidence of post-extubation dysphagia. RESULTS: A total of 231 critically ill adult coronavirus disease 2019 positive patients were included, and 81 patients remained in the final analysis after exclusion criteria were applied (e.g. patients transferred). Dysphagia screening positivity was 25 of 81 (30.9 per cent), with 28.2 per cent (22 of 78) having confirmed dysphagia by specialist examination within 24 hours (n = 3 lost to follow up). CONCLUSION: In this observational study, it was observed that the incidence of dysphagia in adult critically ill coronavirus disease 2019 patients was about 31 per cent (i.e. increased when compared with a historical pre-pandemic non-coronavirus disease 2019 intensive care unit cohort).

Data on Transfer of Human Coronavirus SARS-CoV-2 from Foods and Packaging Materials to Gloves Indicate That Fomite Transmission Is of Minor Importance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly transmitted via droplets and aerosols. To evaluate the role of transmission by fomites, SARS-CoV-2-specific data on transfer rates from surfaces to hands and from hands to face are lacking. Here, we generated quantitatively controlled transfer rates for SARS-CoV-2 from food items (lettuce, ham, and vegetarian meat alternative [VMA]) and packaging materials (cardboard and plastic) to gloves using a wet, dry, and frozen viral inoculum and from glove to glove using a wet viral inoculum. For biosafety reasons, the transfer from surfaces to hands and hands to face was simulated by using gloves. The cumulative transfer rate was calculated by using the data from the first transfer experiment, food or packaging material to glove, and combined with the transfer rate obtained from the second transfer experiment from glove to glove. The cumulative transfer rates from lettuce (4.7%) and ham (3.4%) were not significantly different (P > 0.05) but were significantly higher (P < 0.05) than that from VMA ("wet" or "frozen"). The wet cumulative transfer rate from VMA (1.3%) was significantly higher than the cumulative transfer rate from frozen VMA (0.0011%). No transfer from plastic or cardboard was observed with a dry inoculum. The plastic packaging under wet conditions provided the highest cumulative transfer rate (3.0%), while the cumulative transfer from frozen cardboard was very small (0.035%). Overall, the transfer rates determined in this study suggest a minor role of foods or food packaging materials in infection transmission. IMPORTANCE The observation of SARS-CoV-2 RNA in swab samples from frozen fish packages in China, confirmed only once by cell culture, led to the hypothesis that food contaminated with SARS-CoV-2 virus particles could be the source of an outbreak. Epidemiological evidence for fomites as infection source is scarce, but it is important for the food industry to evaluate this infection path with quantitative microbial risk assessment (QMRA), using measured viral transfer rates from surfaces to hands and face. The present study provides transfer data for SARS-CoV-2 from various types of foods and packaging materials using quantitative methods that take uncertainties related to the virus recovery from the different surfaces into consideration. The transfer data from this model system provide important input parameters for QMRA models to assess the risk of SARS-CoV-2 transmission from contaminated food items.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

[Rescue of injured horses, cattle and pigs from manure and cesspools by the large animal rescue service Switzerland and Liechtenstein (GTRD CH/FL)®]. / Bergung von verunfallten Pferden, Rindern und Schweinen aus Mist- und Jauchegruben durch den Grosstier­rettungsdienst Schweiz und Liechtenstein (GTRD CH/FL)®.

INTRODUCTION: One of the varied tasks of the Large Animal Rescue Service Switzerland and Liechtenstein (GTRD CH/FL)® is the recovery of animals from manure and cesspools. The aim of the present retrospective study was the evaluation of the rescue protocols of the GTRD CH/FL from such operations and the documentation of a rescue procedure. In the past 25 years, a total of 176 animals have been rescued from manure and cesspools. These included 113 cattle, 51 horses and 12 pigs. All animals could be safely rescued with the animal rescue and transport net (TBTN) or the large animal vertical rescue set (GTVBS). The TBTN is used when the opening of the cesspool is large enough to recover the animal in a horizontal position. The GTVBS is particularly suitable for narrow openings, as the recovery in a -vertical position does not require any constructional modification or the enlargement of the cesspool opening. Both rescue harnesses are characterized by reliable handling and allow gentle recovery.

INTRODUCTION: L'une des multiples tâches du Service de sauvetage des grands animaux de Suisse et du Liechtenstein (GTRD CH/FL)® est de sortir des animaux de fosses à fumier ou à lisier. Le but de la présente étude rétrospective était l'évaluation des protocoles de sauvetage du GTRD CH/FL sur la base de ces opérations et la documentation d'un processus de sauvetage. Au cours des 25 dernières années, 176 animaux au total ont été tirés de fosses à fumier ou à lisier. Il s'agissait de 113 bovins, 51 chevaux et 12 porcs. Tous les animaux ont pu être secourus en toute sécurité grâce au filet de sauvetage et de transport des animaux (TBTN) ou à l'équipement de sauvetage vertical pour grands animaux (GTVBS). Le TBTN est utilisé lorsque l'ouverture de la fosse à lisier est suffisamment grande pour récupérer l'animal en position horizontale. Le GTVBS est particulièrement adapté aux ouvertures étroites, car la récupération en position verticale permet de ne pas devoir ou modifier modifiées par d'autres mesures structurelles les ouvertures des fosses. Les deux harnais de sauvetage se caractérisent par une manipulation fiable et permettent une récupération en douceur.

Dynamical disentanglement in an analysis of oscillatory systems: an application to respiratory sinus arrhythmia.

We develop a technique for the multivariate data analysis of perturbed self-sustained oscillators. The approach is based on the reconstruction of the phase dynamics model from observations and on a subsequent exploration of this model. For the system, driven by several inputs, we suggest a dynamical disentanglement procedure, allowing us to reconstruct the variability of the system's output that is due to a particular observed input, or, alternatively, to reconstruct the variability which is caused by all the inputs except for the observed one. We focus on the application of the method to the vagal component of the heart rate variability caused by a respiratory influence. We develop an algorithm that extracts purely respiratory-related variability, using a respiratory trace and times of R-peaks in the electrocardiogram. The algorithm can be applied to other systems where the observed bivariate data can be represented as a point process and a slow continuous signal, e.g. for the analysis of neuronal spiking. This article is part of the theme issue 'Coupling functions: dynamical interaction mechanisms in the physical, biological and social sciences'.

Author Correction: Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

This article contains errors in Figs. 5 and 6, for which we apologize. In Fig. 5f, the image 'E12.5 tail' was inadvertently replaced with a duplicate of the image 'E12.5 trunk' from the same panel. In Figure 6d, the image 'E9.5/OH-TAM E8.5, embryo' was inadvertently replaced with a duplicate of the image 'E10.5/ OH-TAM E8.5, embryo' from Fig. 6b. The corrected versions of these figures appear in the Author Correction associated with this Article.

Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX3CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.

Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Mobilan: a recombinant adenovirus carrying Toll-like receptor 5 self-activating cassette for cancer immunotherapy.

Toll-like receptor 5 (TLR5) is considered an attractive target for anticancer immunotherapy. TLR5 agonists, bacterial flagellin and engineered flagellin derivatives, have been shown to have potent antitumor and metastasis-suppressive effects in multiple animal models and to be safe in both animals and humans. Anticancer efficacy of TLR5 agonists stems from TLR5-dependent activation of nuclear factor-κB (NF-κB) that mediates innate and adaptive antitumor immune responses. To extend application of TLR5-targeted anticancer immunotherapy to tumors that do not naturally express TLR5, we created an adenovirus-based vector for intratumor delivery, named Mobilan that drives expression of self-activating TLR5 signaling cassette comprising of human TLR5 and a secreted derivative of Salmonella flagellin structurally analogous to a clinical stage TLR5 agonist, entolimod. Co-expression of TLR5 receptor and agonist in Mobilan-infected cells established an autocrine/paracrine TLR5 signaling loop resulting in constitutive activation of NF-κB both in vitro and in vivo. Injection of Mobilan into primary tumors of the prostate cancer-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice resulted in a strong induction of multiple genes involved in inflammatory responses and mobilization of innate immune cells into the tumors including neutrophils and NK cells and suppressed tumor progression. Intratumoral injection of Mobilan into subcutaneously growing syngeneic prostate tumors in immunocompetent hosts improved animal survival after surgical resection of the tumors, by suppression of tumor metastasis. In addition, vaccination of mice with irradiated Mobilan-transduced prostate tumor cells protected mice against subsequent tumor challenge. These results provide proof-of-concept for Mobilan as a tool for antitumor vaccination that directs TLR5-mediated immune response toward cancer cells and does not require identification of tumor antigens.

Pull-out strength of patient-specific template-guided vs. free-hand fluoroscopically controlled thoracolumbar pedicle screws: a biomechanical analysis of a randomized cadaveric study.

PURPOSE: To assess the pull-out strength of thoracolumbar pedicle screws implanted via either a patient-specific template-guided or conventional free-hand fluoroscopically controlled technique in a randomized cadaveric study, and to evaluate the influence of local vertebral bone density, quantified by Hounsfield units (HU), on pedicle screw pull-out strength. METHODS: Thoracolumbar pedicles of three spine cadavers were instrumented using either a free-hand fluoroscopically controlled or a patient-specific template-guided technique. Preoperative bone density was quantified by HU measured on CT. Pedicle perforation was evaluated on postoperative CT scans by an independent and blinded radiologist. After dissected vertebrae were embedded in aluminum fixation devices, pull-out testing was initiated with a preload of 50 N and a constant displacement rate of 0.5 mm/s. Subgroup analyses were performed excluding pedicle screws with a pedicle breach (n = 47). RESULTS: Pull-out strength was significantly different with 549 ± 278 and 441 ± 289 N in the template-guided (n = 50) versus fluoroscopically controlled (n = 48) subgroups (p = 0.031), respectively. Subgroup analysis limited to screws with an intrapedicular trajectory revealed a tendency toward a higher pull-out strength in the template-guided (n = 30) versus fluoroscopically controlled screws (n = 21) with 587 ± 309 and 454 ± 269 N (p = 0.118), respectively. There was a trend toward a higher pull-out strength (709 ± 418 versus 420 ± 149 N) in vertebrae with a bone density of (>171 HU) versus (<133 HU), respectively (p = 0.061). CONCLUSIONS: There was a significantly higher pull-out strength of thoracolumbar pedicle screws when inserted via a patient-specific template-guided versus conventional free-hand fluoroscopically controlled technique, potentially associated with screw trajectory.

The cortical spatiotemporal correlate of otolith stimulation: Vestibular evoked potentials by body translations.

The vestibular organ senses linear and rotational acceleration of the head during active and passive motion. These signals are necessary for bipedal locomotion, navigation, the coordination of eye and head movements in 3D space. The temporal dynamics of vestibular processing in cortical structures have hardly been studied in humans, let alone with natural stimulation. The aim was to investigate the cortical vestibular network related to natural otolith stimulation using a hexapod motion platform. We conducted two experiments, 1. to estimate the sources of the vestibular evoked potentials (VestEPs) by means of distributed source localization (n=49), and 2. to reveal modulations of the VestEPs through the underlying acceleration intensity (n=24). For both experiments subjects were accelerated along the main axis (left/right, up/down, fore/aft) while the EEG was recorded. We were able to identify five VestEPs (P1, N1, P2, N2, P3) with latencies between 38 and 461 ms as well as an evoked beta-band response peaking with a latency of 68 ms in all subjects and for all acceleration directions. Source localization gave the cingulate sulcus visual (CSv) area and the opercular-insular region as the main origin of the evoked potentials. No lateralization effects due to handedness could be observed. In the second experiment, area CSv was shown to be integral in the processing of acceleration intensities as sensed by the otolith organs, hinting at its potential role in ego-motion detection. These robust VestEPs could be used to investigate the mechanisms of inter-regional interaction in the natural context of vestibular processing and multisensory integration.

Peri- and postinterventional antithrombotic therapy in TAVI. Do we need antiplatelet therapy?

Interventional treatment of aortic valve stenosis by transcatheter aortic valve replacement (TAVR) has become routine practice in elderly and high risk patients in recent years. Similar to other vascular interventional or surgical procedures TAVR carries thrombotic risks such as stroke, myocardial infarction or systemic embolism as well as peri-procedural bleeding risks. These risks comprise the access site, the type of prosthesis, and the individual risk profile of the patient. Not only during the peri-procedural period but also during longterm follow-up the current target population for TAVR procedures carries a high risk for thrombotic events in particular if atrial fibrillation is present. On the other hand side the bleeding risk is also increased in these patients. Thus, to provide the optimal strategy of antithrombotic therapy during and after TAVR remains a clinical challenge.

Prospective observational study of emergency airway management in the critical care environment of a tertiary hospital in Melbourne.

The objective of this study is to describe the population of patients receiving emergency airway management outside operating theatres at our institution, a tertiary referral centre in Melbourne. A registry of all patients receiving emergency airway management in the emergency department, ICU and on the wards as part of Medical Emergency Response teams' care, was prospectively collected. There were 128 adults and one paediatric patient requiring emergency airway management recruited to the study. Data for analysis included patient demographics, pre-oxygenation and apnoeic oxygenation, staff, drugs, details of laryngoscopic attempts, adjuncts, airway manoeuvres, complications sustained and method of confirmation of endotracheal tube placement. Over a 12-month period, there were 139 intubations of 129 patients, requiring a total of 169 attempts. Respiratory failure was the most common indication for intubation. Intubation was successful on the first episode of laryngoscopy in 116 (83.5%) patients. Complications occurred in 48 patients. In the cohort of patients without respiratory failure, nasal cannulae apnoeic oxygenation significantly reduced the incidence of hypoxaemia (0 out of 31 [0.0%] versus 10 out of 60 [16.7%], P=0.016; absolute risk reduction 16.7%; number needed to treat: 6). Waveform capnography was used to confirm endotracheal tube placement in 133 patients and there were four episodes of oesophageal intubation, all of which were recognised immediately. In the critical care environment of our institution, emergency airway management is achieved with a first-attempt success rate that is comparable to overseas data. Nasal cannulae apnoeic oxygenation appears to significantly reduce the risk of hypoxaemia in patients without respiratory failure and the use of waveform capnography eliminates episodes of unrecognised oesophageal intubation.

Electrically induced muscle cramps induce hypertrophy of calf muscles in healthy adults.

OBJECTIVES: Skeletal muscles usually cramp at short lengths, where the tension that can be exerted by muscle fibers is low. Since high tension is an important anabolic stimulus, it is questionable if cramps can induce hypertrophy and strength gains. In the present study we investigated if electrically induced cramps (EIMCs) can elicit these adaptations. METHODS: 15 healthy male adults were randomly assigned to an intervention (IG; n=10) and a control group (CG; n=5). The cramp protocol (CP) applied twice a week to one leg of the IG, consisted of 3x6 EIMCs, of 5 s each. Calf muscles of the opposite leg were stimulated equally, but were hindered from cramping by fixating the ankle at 0° plantar flexion (nCP). RESULTS: After six weeks, the cross sectional area of the triceps surae was similarly increased in both the CP (+9.0±3.4%) and the nCP (+6.8±3.7%). By contrast, force of maximal voluntary contractions, measured at 0° and 30° plantar flexion, increased significantly only in nCP (0°: +8.5±8.8%; 30°: 11.7±13.7%). CONCLUSION: The present data indicate that muscle cramps can induce hypertrophy in calf muscles, though lacking high tension as an important anabolic stimulus.

Electrochemical and physicochemical properties of small phosphonium cation ionic liquid electrolytes with high lithium salt content.

Electrolytes of a room temperature ionic liquid (RTIL), trimethyl(isobutyl)phosphonium (P111i4) bis(fluorosulfonyl)imide (FSI) with a wide range of lithium bis(fluorosulfonyl)imide (LiFSI) salt concentrations (up to 3.8 mol kg(-1) of salt in the RTIL) were characterised using a combination of techniques including viscosity, conductivity, differential scanning calorimetry (DSC), electrochemical impedance spectroscopy (EIS), nuclear magnetic resonance (NMR) and cyclic voltammetry (CV). We show that the FSI-based electrolyte containing a high salt concentration (e.g. 1 : 1 salt to IL molar ratio, equivalent to 3.2 mol kg(-1) of LiFSI) displays unusual transport behavior with respect to lithium ion mobility and promising electrochemical behavior, despite an increase in viscosity. These electrolytes could compete with the more traditionally studied nitrogen-based ionic liquids (ILs) in lithium battery applications.

Ionoacoustic characterization of the proton Bragg peak with submillimeter accuracy.

PURPOSE: Range verification in ion beam therapy relies to date on nuclear imaging techniques which require complex and costly detector systems. A different approach is the detection of thermoacoustic signals that are generated due to localized energy loss of ion beams in tissue (ionoacoustics). Aim of this work was to study experimentally the achievable position resolution of ionoacoustics under idealized conditions using high frequency ultrasonic transducers and a specifically selected probing beam. METHODS: A water phantom was irradiated by a pulsed 20 MeV proton beam with varying pulse intensity and length. The acoustic signal of single proton pulses was measured by different PZT-based ultrasound detectors (3.5 and 10 MHz central frequencies). The proton dose distribution in water was calculated by Geant4 and used as input for simulation of the generated acoustic wave by the matlab toolbox k-WAVE. RESULTS: In measurements from this study, a clear signal of the Bragg peak was observed for an energy deposition as low as 10(12) eV. The signal amplitude showed a linear increase with particle number per pulse and thus, dose. Bragg peak position measurements were reproducible within ±30 µm and agreed with Geant4 simulations to better than 100 µm. The ionoacoustic signal pattern allowed for a detailed analysis of the Bragg peak and could be well reproduced by k-WAVE simulations. CONCLUSIONS: The authors have studied the ionoacoustic signal of the Bragg peak in experiments using a 20 MeV proton beam with its correspondingly localized energy deposition, demonstrating submillimeter position resolution and providing a deep insight in the correlation between the acoustic signal and Bragg peak shape. These results, together with earlier experiments and new simulations (including the results in this study) at higher energies, suggest ionoacoustics as a technique for range verification in particle therapy at locations, where the tumor can be localized by ultrasound imaging. This acoustic range verification approach could offer the possibility of combining anatomical ultrasound and Bragg peak imaging, but further studies are required for translation of these findings to clinical application.

Activation patterns of different brain areas during incremental exercise measured by near-infrared spectroscopy.

Recent studies postulated that increased oxygenation of the prefrontal cortex (PFC) during elevating exercise intensities reflects a specific activation of this region. Furthermore, the drop in PFC oxygenation often measured shortly before exhaustion is interpreted as a main factor limiting exercise. Nevertheless, a limitation of these studies is that they often measured NIRS only in the PFC. Within this study, we hypothesized that these findings are not region specific but rather result from systemic blood redistribution to the working skeletal muscle. NIRS was measured in three different brain regions and the working skeletal muscle during incremental cycling till exhaustion in nine healthy men. Oxygenated hemoglobin of the PFC increased from low to submaximal intensities and leveled off at maximal intensities. There was no drop in PFC oxygenation before exercise abortion. Interestingly, the occipital cortex was unaffected during exercise, while the motor cortex showed an increasing deoxygenation with elevating exercise intensities, just as observed in the skeletal muscle. In conclusion, this study does not support the notion that PFC deoxygenation is involved in the limitation of maximum exercise capacity. Against the hypothesis, the NIRS signals of the other cortices differed clearly, indicating that the previously reported findings indeed represent region-specific activations.