[Comparison of hospital rating websites among each other and with data from hospital quality reports and quality assurance based on routine data]. / Vergleich von Patientenbewertungen auf Online-Portalen untereinander und mit Qualitätsberichten der Krankenhäuser und der Qualitätssicherung mit Routinedaten.

BACKGROUND: In addition to the objectifiable treatment quality, patients' perspectives are gaining relevance. OBJECTIVE: This study aimed to characterize available hospital rating websites (HRW) with regards to patient ratings and to compare them with data from hospital quality reports and quality assurance based on routine data (QSR) for urological departments. MATERIALS AND METHODS: After a structured online search for HRWs, websites were compared based on patient ratings from the 10 urologic departments with the largest intervention rates in 2021 using generalized estimated equations. For radical prostatectomy (RPE), quantitative comparison of patient ratings (klinikbewertungen.de) and QSR-based ratings was performed using Spearman's rank correlation. RESULTS: Of 1845 hits, 25 portals were analyzed. The department-wise comparison of HRWs resulted in significantly different patient ratings (p < 0.001). Patient ratings (klinikbewertungen.de) and QSR data (AOK-Gesundheitsnavigator) showed no significant correlation. An internal comparison of QSR data and patient ratings from the AOK-Gesundheitsnavigator on RPE showed a significant negative correlation between the overall rating and unplanned reoperations (r = -0.81) or other complications (r = -0.91). There was no significant correlation with the recommendation rate by patients. CONCLUSION: Hospital rating websites show considerable heterogeneity regarding patient ratings of the same urology department in different portals. Furthermore, based on the selected examples, there seems to be no correlation between subjective and objective evaluations between different websites or within one website.

Interdisciplinary perspectives on computed tomography in sepsis: survey among medical doctors at a large university medical center.

OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.

Age and gender effects on non-suicidal self-injury, and their interplay with psychological distress.

INTRODUCTION: NSSI (non-suicidal self-injury) is an important public health issue, with high prevalence and associations with future mental illness and suicide. To date, no large single study has tested age and gender effects on NSSI and their interplay with psychological distress. METHOD: NSSI and psychological distress were ascertained by questionnaire in a community study of 2368 young people aged 14-25; proportions at each age and of each gender were approximately equal. RESULTS: There was a significant quadratic interaction between age and gender on last month NSSI prevalence (p = 0.025): NSSI was more common in females ages 16-19, but there were no significant gender differences at younger/older ages. General distress partially mediated the effects of age and gender on NSSI. The association between general distress and NSSI was not significantly moderated by age, gender nor their interactions. CONCLUSIONS: Gender difference in NSSI is not a static gap, but evolves across time, widening in mid-adolescence and disappearing by early adulthood. Part of the reason for that gender gap being present at those ages is the increase levels of distress in young women at those ages. There was no evidence that the effects of general distress on NSSI differed by age/gender.

Microfluidic chip connected to porous microneedle array for continuous ISF sampling.

Minimally invasive biosensing using microneedles (MNs) is a desirable technology for continuous healthcare monitoring. Among a wide range of MNs, porous MNs are expected to be applied for sampling of interstitial fluids (ISF) by connecting the internal tissue to external measurement devices. In order to realize a continuous measurement of biomarkers in ISF through porous MNs, their integration with a microfluidic chip is a promising approach due to its applicability to micro-total analysis system (µTAS) technology. In this study, we developed a fluidic system to directly interface porous MNs to a microfluidic chip consisting of a capillary pump for the continuous sampling of ISF. The porous and flexible MNs made of PDMS are connected to the microfluidic chip fabricated by standard microelectro-mechanical system (MEMS) processes, showing a continuous flow of phosphate buffered saline (PBS). The developed device will lead to the minimally invasive and continuous biosampling for long-term healthcare monitoring.

Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordingsin vivo.

Objective.Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes.Approach.We report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-µm-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e. grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse forin vivorecordings of freely behaving animals.Main results.Probes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiologicalin vivorecordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone.Significance.The innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan-style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-µm-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

Multifunctional optrode for opsin delivery, optical stimulation, and electrophysiological recordings in freely moving rats.

Objective. Optogenetics involves delivery of light-sensitive opsins to the target brain region, as well as introduction of optical and electrical devices to manipulate and record neural activity, respectively, from the targeted neural population. Combining these functionalities in a single implantable device is of great importance for a precise investigation of neural networks while minimizing tissue damage.Approach. We report on the development, characterization, andin vivovalidation of a multifunctional optrode that combines a silicon-based neural probe with an integrated microfluidic channel, and an optical glass fiber in a compact assembly. The silicon probe comprises an 11-µm-wide fluidic channel and 32 recording electrodes (diameter 30µm) on a tapered probe shank with a length, thickness, and maximum width of 7.5 mm, 50µm, and 150µm, respectively. The size and position of fluidic channels, electrodes, and optical fiber can be precisely tuned according to thein vivoapplication.Main results.With a total system weight of 0.97 g, our multifunctional optrode is suitable for chronicin vivoexperiments requiring simultaneous drug delivery, optical stimulation, and neural recording. We demonstrate the utility of our device in optogenetics by injecting a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequent photostimulation of the transduced neurons while recording neural activity from both the target and adjacent regions in a freely moving rat for up to 9 weeks post-implantation. Additionally, we demonstrate a pharmacological application of our device by injecting GABA antagonist bicuculline in an anesthetized rat brain and simultaneously recording the electrophysiological response.Significance. Our triple-modality device enables a single-step optogenetic surgery. In comparison to conventional multi-step surgeries, our approach achieves higher spatial specificity while minimizing tissue damage.

Droplet digital PCR allows vector copy number assessment and monitoring of experimental CAR T cells in murine xenograft models or approved CD19 CAR T cell-treated patients.

BACKGROUND: Genetically engineered chimeric antigen receptor (CAR) T lymphocytes are promising therapeutic tools for cancer. Four CAR T cell drugs, including tisagenlecleucel (tisa-cel) and axicabtagene-ciloleucel (axi-cel), all targeting CD19, are currently approved for treating B cell malignancies. Flow cytometry (FC) remains the standard for monitoring CAR T cells using a recombinant biotinylated target protein. Nevertheless, there is a need for additional tools, and the challenge is to develop an easy, relevant, highly sensitive, reproducible, and inexpensive detection method. Molecular tools can meet this need to specifically monitor long-term persistent CAR T cells. METHODS: Based on 2 experimental CAR T cell constructs, IL-1RAP and CS1, we designed 2 quantitative digital droplet (ddPCR) PCR assays. By targeting the 4.1BB/CD3z (28BBz) or 28/CD3z (28z) junction area, we demonstrated that PCR assays can be applied to approved CD19 CAR T drugs. Both 28z and 28BBz ddPCR assays allow determination of the average vector copy number (VCN) per cell. We confirmed that the VCN is dependent on the multiplicity of infection and verified that the VCN of our experimental or GMP-like IL-1RAP CAR T cells met the requirement (< 5 VCN/cell) for delivery to the clinical department, similar to approved axi-cel or tisa-cel drugs. RESULTS: 28BBz and 28z ddPCR assays applied to 2 tumoral (acute myeloid leukemia (AML) or multiple myeloma (MM) xenograft humanized NSG mouse models allowed us to quantify the early expansion (up to day 30) of CAR T cells after injection. Interestingly, following initial expansion, when circulating CAR T cells were challenged with the tumor, we noted a second expansion phase. Investigation of the bone marrow, spleen and lung showed that CAR T cells disseminated more within these tissues in mice previously injected with leukemic cell lines. Finally, circulating CAR T cell ddPCR monitoring of R/R acute lymphoid leukemia or diffuse large B cell lymphoma (n = 10 for tisa-cel and n = 7 for axi-cel) patients treated with both approved CAR T cells allowed detection of early expansion, which was highly correlated with FC, as well as long-term persistence (up to 450 days), while FC failed to detect these events. CONCLUSION: Overall, we designed and validated 2 ddPCR assays allowing routine or preclinical monitoring of early- and long-term circulating approved or experimental CAR T cells, including our own IL-1RAP CAR T cells, which will be evaluated in an upcoming phase I clinical trial.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Associations between baseline cortisol and trajectory of symptom improvement in depressed adolescents receiving psychological therapy.

BACKGROUND: Cortisol hypersecretion in depressed adolescents and adults is associated with more persistent illness and may signal a lower response to psychological therapies. A meta-analysis of small and heterogenous studies demonstrated that higher pre-treatment basal cortisol levels were associated with poorer response specifically to psychological therapy for depression. The objective of this study was to investigate the relationship between both morning and evening salivary cortisol levels and response to psychological therapy in depressed adolescents participating in one large randomised controlled trial. METHODS: We tested the association between morning and evening salivary cortisol levels at baseline and improvement in depressive symptoms in response to psychological therapies in depressed adolescents at 6 time points: baseline, 6, 12, 36, 52- and 86-weeks post-randomisation, using the self-reported Mood and Feelings Questionnaire (MFQ). RESULTS: High evening cortisol was associated with a slower initial decline in depressive symptoms (cortisol x quadratic time p = .022); however it was not associated with total change in depressive symtoms over the whole course of the study. Morning cortisol was not associated with change in depressive symptoms. These effects were not significantly different across the three psychological therapies. LIMITATIONS: Results may not generalize to adolescents receiving other treatments (medication) or no treatment, and may not generalize to adults. Only a minority of eligible participants collected valid cortisol samples. CONCLUSIONS: Higher pretreatment evening cortisol may impair a depressed adolescent's ability to use psychological therapy.

[Parental Resolution of the Child's Disability Diagnosis in the Reaction to Diagnosis Interview (RDI) and Effects on the Play Interaction with the Child]. / Diagnoseverarbeitung von Eltern behinderter Kinder im Reaction to Diagnosis Interview (RDI) und Auswirkungen auf das Spiel mit dem Kind.

Parental Resolution of the Child's Disability Diagnosis in the Reaction to Diagnosis Interview (RDI) and Effects on the Play Interaction with the Child Examining 37 qualitative interviews with mothers and fathers of a child with intellectual disability it was observed that the emotions and traumatic experiences, associated with the child's diagnosis, still burden the relationship with the child even after several years, so that many affected cannot come to resolution. On the other hand, resolution of the diagnosis was indicated for 65 % of the parents, enabling them to reclaim lost space for building a relationship with their child. While these parents significantly more often report purposeless and responsive play interaction with their children, non-resolved parents still seem to be driven to counteract the disability by playing educational games or playing games, which promote the development. In a parallel music therapeutic study, the effects of parental resolution also are monitored in children's free play interaction: Children of resolved parents interact more often in a dialogic relationship, whereas children of non-resolved parents are less able to balance dyadic turn-taking and interaction control in free music play.

Customized Thinning of Silicon-based Neural Probes Down to 2 µm.

This paper reports on the customized thinning of neural probes based on silicon (Si) using deep reactive ion etching (DRIE) as a post-processing step. The reduced probe dimensions are expected to minimize local tissue trauma, while guaranteeing probe integrity during implantation. For DRIE, the probes are partially masked by a micromachined Si cover chip comprising tailored cavities enabling any desired thinned length l and probe thickness t by a proper choice of cover chip design and DRIE parameters, respectively. A broad variety of probe designs were realized with shank tip thicknesses ranging from 35 µm down to 2 µm. All probes could successfully be implanted into a brain tissue phantom, demonstrating a pronounced reduction in insertion force from 0.55 mN for unprocessed probes to 0.08 mN for 2-µm-thin shanks. When the dura mater was mimicked by a polyethylene (PE) membrane, forces were reduced from 28.9 mN to 16.6 mN for 15-µm-thin shanks.

Multichannel optogenetic stimulation of the auditory pathway using microfabricated LED cochlear implants in rodents.

When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)-expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-µm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system.

µLED-based optical cochlear implants for spectrally selective activation of the auditory nerve.

Electrical cochlear implants (eCIs) partially restore hearing and enable speech comprehension to more than half a million users, thereby re-connecting deaf patients to the auditory scene surrounding them. Yet, eCIs suffer from limited spectral selectivity, resulting from current spread around each electrode contact and causing poor speech recognition in the presence of background noise. Optogenetic stimulation of the auditory nerve might overcome this limitation as light can be conveniently confined in space. Here, we combined virus-mediated optogenetic manipulation of cochlear spiral ganglion neurons (SGNs) and microsystems engineering to establish acute multi-channel optical cochlear implant (oCI) stimulation in adult Mongolian gerbils. oCIs based on 16 microscale thin-film light-emitting diodes (µLEDs) evoked tonotopic activation of the auditory pathway with high spectral selectivity and modest power requirements in hearing and deaf gerbils. These results prove the feasibility of µLED-based oCIs for spectrally selective activation of the auditory nerve.

Composition of browses consumed by Matschie's tree kangaroo (Dendrolagus matschiei) sampled from home ranges in Papua New Guinea.

Twenty-six samples (n = 24 spp.) of foods eaten, including ferns, shrubs, vines, orchids, herbaceous plants, and tree leaves, were collected from the Yopno, Uruwa, and Som Conservation Area at approximately 1,800 m altitude on the Huon Peninsula, Papua New Guinea (PNG). Samples were weighed fresh in the field and transported to the Lae National Herbarium in PNG for drying and confirmed identification, before transporting to the US for analysis of primary nutrient composition and minerals. Water content averaged 76 ± 10% (mean ± standard deviation); on a dry matter (DM) basis, foods averaged moderate protein (11 ± 5%), and soluble carbohydrate (27 ± 8%) content, along with exceptionally low starch (1 ± 1%) and crude fat (3 ± 2%) values, and moderate to high values in fiber fractions (neutral detergent fiber 52 ± 13%, acid detergent fiber 39 ± 10%, lignin 15 ± 6%). Calculated metabolizable energy content of native forages averaged 1.9 ± 0.3 Mcal/kg DM (ruminant model). Macromineral concentrations (DM basis) were not exceptional (calcium 1.1 ± 1.0%, phosphorus 0.2 ± 0.1%, magnesium 0.3 ± 0.2%, potassium 1.8 ± 0.9%, sodium 0.02 ± 0.02%), and select trace minerals were within anticipated ranges for herbivores (copper 12 ± 13 mg/kg, iron 48 ± 26 mg/kg, zinc 34 ± 18 mg/kg) with the exception of manganese (268 ± 225 mg/kg), which could be considered on the high end of dietary adequacy for most herbivores. These data provide useful information that can be used to adjust nutrient targets for dietary development and feeding management of captive populations of tree kangaroos.

High-density electrophysiological recordings in macaque using a chronically implanted 128-channel passive silicon probe.

OBJECTIVE: The analysis of interactions among local populations of neurons in the cerebral cortex (e.g. within cortical microcolumns) requires high resolution and high channel count recordings from chronically implanted laminar microelectrode arrays. The request for high-density recordings of a large number of recording sites can presently only be accomplished by probes realized using complementary metal-oxide-semiconductor (CMOS) technology. In preparation for their use in non-human primates, we aimed for neural probe validation in a head-fixed approach analyzing the long-term recording capability. APPROACH: We examined chronically implanted silicon-based laminar probes, realized using a CMOS technology in combination with micromachining, to record from the primary visual cortex (V1) of a monkey. We used a passive CMOS probe that had 128 electrodes arranged at a pitch of 22.5 µm in four columns and 32 rows on a slender shank. In order to validate the performance of a dedicated microdrive, the overall dimensions of probe and interface boards were chosen to be compatible with the final active CMOS probe comprising integrated circuitry. MAIN RESULTS: Using the passive probe, we recorded simultaneously local field potentials (LFP) and spiking multiunit activity (MUA) in V1 of an awake behaving macaque monkey. We found that an insertion through the dura and subsequent readjustments of the chronically implanted neural probe was possible and allowed us to record stable LFPs for more than five months. The quality of MUA degraded within the first month but remained sufficiently high to permit mapping of receptive fields during the full recording period. SIGNIFICANCE: We conclude that the passive silicon probe enables semi-chronic recordings of high quality of LFP and MUA for a time span exceeding five months. The new microdrive compatible with a commercial recording chamber successfully demonstrated the readjustment of the probe position while the implemented plug structure effectively reduced brain tissue movement relative to the probe.

Compact Optical Neural Probes With Up to 20 Integrated Thin-Film µLEDs Applied in Acute Optogenetic Studies.

This paper reports on the development, characterization and in vivo validation of compact optical neural probes. These novel intracerebral devices comprise micro light-emitting diodes ( µLEDs) integrated along their slender probe shanks with up to 20 µLEDs per device. Blue light with a peak wavelength of 455 nm is emitted from circular apertures 100 µm in diameter. The µLEDs are structured on GaN-on-sapphire wafers and subsequently transferred onto silicon (Si) carrier wafers. The wafer-scale transfer process provides the opportunity to process the functional GaN layer stack from both sides and hence enables maximizing the efficiency of the µLEDs. Combined with standard MEMS fabrication processes for Si, linear µLED arrays with small inter- µLED distances are achieved on thin probe shanks with cross-sections measuring [Formula: see text]. Devices are interconnected using highly flexible polyimide cables in order to mechanically decouple them from the peripheral electronics during in vivo experiments. Assembled probes emit a peak optical radiant flux of 440 µW (emittance 56 mW mm -2) at 5 mA driving current. Thermal characterization of test probes reveals a temperature increase of 1.5 K measured using an integrated thermistor. Electrical functionality stress tests have been carried out to evaluate the device passivation against the physiological environment. It is estimated to endure at least 48 h during continuously pulsed µLED operation. A compact driving circuitry enables low-noise µLED operation in in vivo optogenetic experiments. The radiant flux necessary to elicit an acceptable neuronal response is determined between 1.36 µW and 17.5 µW. Probe validation successfully demonstrates the layer-specific stimulation in the cortex in multiple in vivo trials.

CMOS-Compatible, Flexible, Intracortical Neural Probes.

Flexible intracortical neural probes elicit a lower foreign body response when compared to rigid implants. However, by incorporating complementary metal-oxide-semiconductor (CMOS) circuitry, silicon-based neural probes can offer an improved scalability and more functionalities than any other currently available technology. OBJECTIVE: Our goal is the development of a novel neural probe that combines flexibility with the functionalities of active CMOS-based probes. METHODS: We interface CMOS-based probe tips of only a few millimeters in length with flexible polyimide cables, which enable the complete implantation of the tips into brain tissue. The multilayer platinum metallization of the cables is patterned using a novel combination of ion beam and plasma etching. Implantation of the flexible probes is verified in brain models using stiff insertion shuttles. RESULT: We assembled neural probes from passive and active tips as short as 1.5 mm and less than 180 µm in width. Active probes feature electrode arrays with 72 recording sites and multiplexing to 16 parallel output lines. We reliably patterned cables with signal lines of 2 µm in width and 3 µm in spacing. Ion beam etching deteriorated the composition of the polyimide substrate and its resistance to around 1 kΩ. An additional plasma treatment re-established high insulation resistances and recovered the chemical composition. Probes were successfully implanted to a depth of 7 mm using insertion shuttles and withstood forces of 63 mN. CONCLUSIONS: This study presents the methods required for the fabrication and application of a new generation of neural probes. SIGNIFICANCE: The synergetic approach surpasses the limitation of each individual probe technology and should be considered in future developments.

Thermodilution vs estimated Fick cardiac output measurement in an elderly cohort of patients: A single-centre experience.

AIMS: Patients referred to the cath-lab are an increasingly elderly population. Thermodilution (TD, gold standard) and the estimated Fick method (eFM) are interchangeably used in the clinical routine to measure cardiac output (CO). However, their correlation in an elderly cohort of cardiac patients has not been tested so far. METHODS: A single, clinically-indicated right heart catheterization was performed on each patient with CO estimated by eFM and TD in 155 consecutive patients (75.1±6.8 years, 57.7% male) between April 2015 and August 2017. Whole Body Oxygen Consumption (VO2) was assumed by applying the formulas of LaFarge (LaF), Dehmer (De) and Bergstra (Be). CO was indexed to body surface area (Cardiac Index, CI). RESULTS: CI-TD showed an overall moderate correlation to CI-eFM as assessed by LaF, De or Be (r2 = 0.53, r2 = 0.54, r2 = 0.57, all p < .001, respectively) with large limits of agreement (-0.64 to 1.09, -1.07 to 0.77, -1.38 to 0.53 l/m2/min, respectively). The mean difference of CI between methods was 0.22, -0.15 and -0.42 (all p<0.001 for difference to TD), respectively. A rate of error ≥20% occurred with the equations by LaF, De or Be in 40.6%, 26.5% and 36.1% of patients, respectively. A CI <2.2 l/m2min was present in 42.6% of patients according to TD and in 60.0%, 31.0% and in 16.1% of patients according to eFM by the formulas of LaF, De or Be. CONCLUSION: Although CI-eFM shows an overall reasonable correlation with CI-TD, the predictive value in a single patient is low. CI-eFM cannot replace CI-TD in elderly patients.

In vivo Recording Quality of Mechanically Decoupled Floating Versus Skull-Fixed Silicon-Based Neural Probes.

Throughout the past decade, silicon-based neural probes have become a driving force in neural engineering. Such probes comprise sophisticated, integrated CMOS electronics which provide a large number of recording sites along slender probe shanks. Using such neural probes in a chronic setting often requires them to be mechanically anchored with respect to the skull. However, any relative motion between brain and implant causes recording instabilities and tissue responses such as glial scarring, thereby shielding recordable neurons from the recording sites integrated on the probe and thus decreasing the signal quality. In the current work, we present a comparison of results obtained using mechanically fixed and floating silicon neural probes chronically implanted into the cortex of a non-human primate. We demonstrate that the neural signal quality estimated by the quality of the spiking and local field potential (LFP) recordings over time is initially superior for the floating probe compared to the fixed device. Nonetheless, the skull-fixed probe also allowed long-term recording of multi-unit activity (MUA) and low frequency signals over several months, especially once pulsations of the brain were properly controlled.

Microfluidic chip to interface porous microneedles for ISF collection.

Porous microneedles (MNs) are expected to be applied for diagnostic microfluidic devices such as blood glucose monitoring as they enable a pain-free penetration of human skin and the extraction of interstitial fluids. However, conventional microfluidic systems require additional steps to separate the liquid from a porous structure used for fluid extraction. In this study, we developed a microfluidic system with a hydrodynamically designed interface between a porous MN array and microchannels to enable a direct analysis of liquids extracted by the porous MN array. The microfluidic chip with an interface for the MN array was successfully realized by standard MEMS processes, enabling a liquid flow through the whole microfluidic structure. The porous MN array was fabricated by the salt leaching and molding method, which was integrated with the chip and demonstrated the successful extraction of liquids from an agarose gel-based skin phantom.