Acute effects of lithium augmentation on the kidney in geriatric compared with non-geriatric patients with treatment-resistant depression.

INTRODUCTION: Lithium augmentation (LA) of antidepressants is a first-line therapy option for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients mostly because of the fear of kidney toxicity. The purpose of this study is to investigate estimated glomerular filtration rate (eGFR) changes and number of acute kidney injuries (AKI) using LA in geriatric compared with non-geriatric patients. METHODS: In a prospective multicenter cohort study, eGFR changes were measured in 201 patients with unipolar depression (nage≥65years  = 29; nage<65years  = 172) at baseline and over 2-6 weeks of LA. We used linear mixed models to investigate changes in eGFR upon LA and assessed the number of AKIs, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: Both age groups showed a significant eGFR decline over the course of treatment with lower eGFR in geriatric patients. The lithium serum level (interpretable as "effect of LA") had a significant effect on eGFR decline. Both effects (age group and lithium serum level) on eGFR decline did not influence each other, meaning the effect of LA on eGFR decline did not differ between age groups. Two AKIs were observed in the geriatric age group when serum lithium levels exceeded the therapeutic range of >0.8 mmol/L. CONCLUSION: This is the first study investigating eGFR change and AKI upon LA for TRD in geriatric compared with non-geriatric patients. Our data suggest that LA, as an effective treatment option in geriatric patients, should be closely monitored to avoid AKIs.

Electrocardiographic Changes During Initiation of Lithium Augmentation of Antidepressant Pharmacotherapy.

PURPOSE/BACKGROUND: Lithium augmentation of antidepressants represents a common strategy to overcome treatment resistance in patients with major depressive disorder. The use of lithium has been associated with cardiovascular adverse effects such as QTc prolongation and tachyarrhythmia. Although the previous studies investigated monotherapy with lithium, the aim of this study was to investigate electrocardiographic changes in LA. METHODS/PROCEDURES: A 12-lead surface electrocardiogram (ECG) was obtained from 38 patients with major depressive disorder before and during LA. Changes in heart rate, PQ, QRS and QTc interval, QT dispersion, ST segment, and T- and U-wave alterations were analyzed using a linear mixed model. FINDINGS/RESULTS: The ECG readings of 33 patients were evaluated. Lithium augmentation was not significantly associated with changes in heart rate, QTc, PQ, or QRS interval. We found a significant decrease in QT dispersion. These results were independent of sex, age, stable comedication, and comorbidities. During LA, we observed 9 cases of T-wave alterations and 2 cases of new U waves. CONCLUSIONS: Our data provide no evidence for serious ECG abnormalities at therapeutic serum lithium levels in patients treated with LA. In particular, we did not find evidence for QTc time lengthening or tachyarrhythmia, such as torsades des pointes. The recommended intervals for ECG checks should be considered to detect long-term effects of LA.

Development of screening questions for doctor-patient consultation assessing the quality of life and psychosocial burden of glioma patients: an explorative study.

PURPOSE: Psychosocial screening for glioma patients is challenging because many patients suffer from neurocognitive deficits, which may impair assessment. This study's aim was to exploratively develop three screening questions for unmet needs to prospectively be applicable in patient-doctor consultation. METHODS: Patient interviews, a survey for health-care professionals and a weighted scoring procedure were developed for this study. Six main areas were defined according to main areas of validated questionnaires (psyche, cognition, body, role functioning, social support, unmet needs). Patients and health-care professionals rated the importance of these areas and corresponding items, patients additionally stated whether the issues addressed affected them. RESULTS: A total of 50 patients were included, and 36 health-care professionals participated in the online survey. The three areas (psyche, body and cognition) considered to be most relevant by both, health-care professionals and patients, generated three screening questions. If the patient was affected by the issue addressed with a screening question, a subordinate question from that area that our patient sample considered most important could additionally be asked. The elaborated screening questions are the following: (1) main area psyche: "Has your mood worsened?", (2) main area body: "Do physical changes put a strain on you?", and (3) main area cognition: "Has your memory capacity worsened?" CONCLUSION: These questions represent a basis for further research regarding their application in neuro-oncological clinical routine.

Validating Deep Neural Networks for Online Decoding of Motor Imagery Movements from EEG Signals.

Non-invasive, electroencephalography (EEG)-based brain-computer interfaces (BCIs) on motor imagery movements translate the subject's motor intention into control signals through classifying the EEG patterns caused by different imagination tasks, e.g., hand movements. This type of BCI has been widely studied and used as an alternative mode of communication and environmental control for disabled patients, such as those suffering from a brainstem stroke or a spinal cord injury (SCI). Notwithstanding the success of traditional machine learning methods in classifying EEG signals, these methods still rely on hand-crafted features. The extraction of such features is a difficult task due to the high non-stationarity of EEG signals, which is a major cause by the stagnating progress in classification performance. Remarkable advances in deep learning methods allow end-to-end learning without any feature engineering, which could benefit BCI motor imagery applications. We developed three deep learning models: (1) A long short-term memory (LSTM); (2) a spectrogram-based convolutional neural network model (CNN); and (3) a recurrent convolutional neural network (RCNN), for decoding motor imagery movements directly from raw EEG signals without (any manual) feature engineering. Results were evaluated on our own publicly available, EEG data collected from 20 subjects and on an existing dataset known as 2b EEG dataset from "BCI Competition IV". Overall, better classification performance was achieved with deep learning models compared to state-of-the art machine learning techniques, which could chart a route ahead for developing new robust techniques for EEG signal decoding. We underpin this point by demonstrating the successful real-time control of a robotic arm using our CNN based BCI.

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

Background: Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method: Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results: In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion: This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.

Identification of different pathways of electron injection in dye-sensitised solar cells of electrodeposited ZnO using an indoline sensitiser.

Charge transfer dynamics in fully operational dye sensitised solar cells consisting of an electrolyte or organic spiroOMeTAD in contact with a highly porous electrodeposited ZnO film sensitised with a monolayer of the indoline dye DN216 were observed using ultrafast transient absorption spectroscopy. From the temporal evolution of spectral signatures assigned with the help of spectroelectrochemical experiments to the population and depopulation of initial, transient and final states, a model was completed for the multistep injection of photoexcited electrons from the molecular absorber to the ZnO acceptor. Injection was found to occur via three different paths with three characteristic rates: directly from the dye's lowest unoccupied molecular orbital into the ZnO conduction band (200 fs) and via intermediate molecular dominated and surface dominated hybrid states (2 ps and 10 ps, respectively).

The Role of Psychological Distress in Relapse Prevention of Alcohol Addiction. Can High Scores on the SCL-90-R Predict Alcohol Relapse?

OBJECTIVE: The aim of this study was to identify if psychological distress may contribute to treatment outcome in alcohol-addicted patients during a follow-up period of 5 months after detoxification. METHODS: As part of a prospective, multicenter, randomized study in relapse prevention, patients' levels of psychological distress were assessed using the Symptome Checklist (SCL-90-R). At study inclusion, all patients were detoxified and showed no more withdrawal symptoms. The patients who relapsed during the 5-month follow-up period were compared with those who remained abstinent. Predictors for relapse were investigated in a logistic regression. RESULTS: First, a significant difference in initial psychological distress between patients who stayed abstinent and patients who relapsed was found: following detoxification, patients who relapsed scored significantly higher on the SCL-90-R at study inclusion. In addition, psychological distress differed over time in both groups. Second, patients without relapse showed a larger decrease in some SCL-90-R scales between the beginning and the end of the observation period than patients who relapsed. Third, the logistic regression analyses showed that high scores on the overall score GSI (Global Severity Index) of the SCL-90-R can be seen as a predictor for future relapse. CONCLUSION: The SCL-90-R may be a useful instrument to predict relapse. As our study indicates that high levels of psychological distress increases the risk of relapse, specific interventions may be targeted at this risk factor.

A Self-Synthesis Approach to Perceptual Learning for Multisensory Fusion in Robotics.

Biological and technical systems operate in a rich multimodal environment. Due to the diversity of incoming sensory streams a system perceives and the variety of motor capabilities a system exhibits there is no single representation and no singular unambiguous interpretation of such a complex scene. In this work we propose a novel sensory processing architecture, inspired by the distributed macro-architecture of the mammalian cortex. The underlying computation is performed by a network of computational maps, each representing a different sensory quantity. All the different sensory streams enter the system through multiple parallel channels. The system autonomously associates and combines them into a coherent representation, given incoming observations. These processes are adaptive and involve learning. The proposed framework introduces mechanisms for self-creation and learning of the functional relations between the computational maps, encoding sensorimotor streams, directly from the data. Its intrinsic scalability, parallelisation, and automatic adaptation to unforeseen sensory perturbations make our approach a promising candidate for robust multisensory fusion in robotic systems. We demonstrate this by applying our model to a 3D motion estimation on a quadrotor.

Psychotherapy of Borderline Personality Disorder: Can the Supply Meet the Demand? A German Nationwide Survey in DBT Inpatient and Day Clinic Treatment Facilities.

The present study aimed to assess (1) the amount of inpatient and day clinic DBT treatment places for patients with borderline personality disorder and (2) the relationship between supply and demand in a given study region. Survey of inpatient and day clinic facilities in the German DBT network. 42 inpatient units and day clinics responded, representing 75 % of the DBT network members contacted. These institutions offer 527 DBT treatment places and treat about 2310 patients per year. The mean waiting period prior to treatment was 14.3 weeks. 700 DBT inpatient or day clinic places exist in Germany in 2011. 3000 patients receive DBT inpatient or day clinic treatment per year. This approximates a ratio of 820 borderline patients for one existing DBT inpatient or day clinic place in Germany. The long waiting time reflects the great demand for this treatment and could be interpreted as an imbalance between supply and demand.

Ultrafast charge-transfer reactions of indoline dyes with anchoring alkyl chains of varying length in mesoporous ZnO solar cells.

Dye-sensitized solar cells based on a mesoporous ZnO substrate were sensitized with the indoline derivatives DN91, DN216 and DN285. The chromophore is the same for each of these dyes. They differ from each other in the length of an alkyl chain, which provides a second anchor to the ZnO surface and prolongs cell lifetime. Ultrafast transient absorption measurements reveal a correlation between the length of the alkyl chain and the fastest electron-injection process. The depopulation of the excited state and the associated emergence of the oxidized molecules are dominant spectral features in the transient absorption of the dyes with shorter alkyl chains. A slower picosecond-scale decay proceeds at constant rate for all three derivatives and is assigned to electron transfer into the trap states of ZnO. All assignments are in good agreement with a higher quantum efficiency of charge injection leading to higher short-circuit currents J(sc) for dyes with shorter alkyl chains.

Influence of counter-anions during electrochemical deposition of ZnO on the charge transport dynamics in dye-sensitized solar cells.

Porous ZnO/EosinY films have been electrochemically deposited by oxygen reduction in the presence of a zinc salt from EosinY-containing aqueous solutions, with either chloride or perchlorate as the counter anion. EosinY was removed and the films were sensitised by D149. These electrodes were used for dye-sensitised solar cells (DSCs), and charge transport in the porous network was studied by intensity modulated current/voltage spectroscopy (IMVS/IMPS) and electrochemical impedance spectroscopy (EIS) under illumination. Doping of ZnO during the electrodeposition could be proven by changes in the charge transport in ZnO and could be shown to occur when chloride was used as the counter ion. By using perchlorate as the counter ion, on the other hand, a more reproducible occupation of trap levels was obtained at, however, slightly lower voltages in DSCs whose origin is discussed in detail.

High-resolution electrochemical and topographical imaging using batch-fabricated cantilever probes.

New cantilever probes for combined scanning electrochemical microscopy-atomic force microscopy (SECM-AFM) have been batch-fabricated, and their application to high resolution electrochemical-topographical imaging has been demonstrated. The conical probes yield outstanding quality Faradaic current maps alongside subnm level topographical information as exemplified by the electrochemical imaging of exfoliated graphene and graphite samples. Current mapping reveals significant heterogeneities in the electroactivity of these carbon surfaces that do not directly correlate to topographical features, suggesting the presence of adsorbed chemical contaminants or intrinsic impurities.

Locally enhanced conductivity due to the tetragonal domain structure in LaAlO3/SrTiO3 heterointerfaces.

The ability to control materials properties through interface engineering is demonstrated by the appearance of conductivity at the interface of certain insulators, most famously the {001} interface of the band insulators LaAlO3 and TiO2-terminated SrTiO3 (STO; refs 1, 2). Transport and other measurements in this system show a plethora of diverse physical phenomena. To better understand the interface conductivity, we used scanning superconducting quantum interference device microscopy to image the magnetic field locally generated by current in an interface. At low temperature, we found that the current flowed in conductive narrow paths oriented along the crystallographic axes, embedded in a less conductive background. The configuration of these paths changed on thermal cycling above the STO cubic-to-tetragonal structural transition temperature, implying that the local conductivity is strongly modified by the STO tetragonal domain structure. The interplay between substrate domains and the interface provides an additional mechanism for understanding and controlling the behaviour of heterostructures.

Few negative effects of psychotherapy in a psychiatric day hospital: a follow-up survey to a multiprofessional treatment with acceptance and commitment therapy.

While there are many studies on psychotherapy and its efficacy - in terms of desired outcomes - there is comparatively little evidence on the possible negative effects of psychotherapy. The aim of this study was to investigate the possible negative effects of a multi-professional psychiatric day hospital treatment for patients with mental health disorders based on Acceptance and Commitment Therapy (ACT), including possible confounding factors. Fifty-one patients with a range of psychiatric diagnoses were assessed three months after an ACT-based psychiatric day hospital treatment. Questionnaires were used to measure negative effects of psychotherapy (INEP), subjective quality of life (WHOQOL-BREF), and symptomatology (BDI-II and SCL-90-R). Correlational analyses and group comparisons were performed to determine the relationship between the sum of reported negative effects on the one hand and symptomology, quality of life, and sociodemographic variables (gender, age, diagnosis, education) on the other hand. At least one negative effect out of a list of 18 possible effects was reported by 45% of participants, and 10% reported more than two. The number of negative effects reported correlates positively with symptomology and negatively with quality of life. The sum of reported negative effects does not correlate with age or gender and does not vary by education level and primary diagnosis. In the light of previous findings, patients included in this study showed lower rates of negative effects, both overall and at item level. Practical implications of these findings are discussed.

DR.BEAT: Initial Functional Testing of a BCG Wearable Prototype for Recording Ballistocardiographic Signals.

DR.BEAT ("Digital Research on Ballistocardiography for Extraterrestrial And Terrestrial use") develops a miniaturized sensor system with signal processing to interpret ballistocardiographic signals and implements an application oriented user interface. Presented is a breadboard prototype's functional tests with regard to data completeness and plausibility. The analysis confirmed a reliability of 99.99995% over the tests and the signals displayed the expected heart-specific characteristics. These results support the ethical justifiability of an initial study.

Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms.

Ultrafast photodynamics of the indoline dye D149 adsorbed to porous ZnO in dye-sensitized solar cells.

We investigate the ultrafast dynamics of the photoinduced electron transfer between surface-adsorbed indoline D149 dye and porous ZnO as used in the working electrodes of dye-sensitized solar cells. Transient absorption spectroscopy was conducted on the dye in solution, on solid state samples and for the latter in contact to a I(-)/I(3)(-) redox electrolyte typical for dye-sensitized solar cells to elucidate the effect of each component in the observed dynamics. D149 in a solution of 1:1 acetonitrile and tert-butyl alcohol shows excited-state lifetimes of 300±50 ps. This signature is severely quenched when D149 is adsorbed to ZnO, with the fastest component of the decay trace measured at 150±20 fs due to the charge-transfer mechanism. Absorption bands of the oxidized dye molecule were investigated to determine regeneration times which are in excess of 1 ns. The addition of the redox electrolyte to the system results in faster regeneration times, of the order of 1 ns.

DR.BEAT: First Insights into a Study to Collect Baseline BCG Data with a Sensor-Based Wearable Prototype in Heart-Healthy Adults.

The DR.BEAT project aims at the further development of a measurement system for recording ballistocardiographic signals into a body-worn sensor system combined with extensive signal processing, data evaluation and visualization. With a first breadboard prototype, an explorative feasibility study for acquiring initial signals of healthy cardiac activity in adults was performed. This paper briefly presents the DR.BEAT project, the breadboard prototype, the study conducted, and initial insights into the study results. The signals obtained in the study exhibit the seismocardiographic characteristics as reported in the literature and form the basis for further development of the hardware as well as the pre-processing and automated analysis algorithms in the DR.BEAT project.Clinical Relevance- The characteristics of ballisto- and seismocardiographic signals allow to infer about the mechanical work of the heart. The development of a body-worn sensor system to record ballisto- and seismocardiographic signals, compact enough for everyday wear, enables the acquisition of heart-specific parameters in terrestrial as well as extraterrestrial application scenarios. Combined with extensive signal analysis and visualization, it holds the potential to monitor heart health in a variety of contexts and support its maintenance and improvement.

Efficacy and safety of levetiracetam for the prevention of alcohol relapse in recently detoxified alcohol-dependent patients: a randomized trial.

BACKGROUND: Antiepileptics have been shown to reduce alcohol intake or to prevent relapse in patients with alcoholism. GOAL: To investigate if the new antiepileptic levetiracetam (LEV) prevents relapse after detoxification compared with placebo in patients with alcohol dependence. METHODS: Two hundred one patients were included in the prospective, randomized, double-blind, multicenter, placebo-controlled trial. After detoxification treatment and a screening period of 7 days, patients were randomized to treatment with LEV or placebo. Medication was administered in a fixed-dose schedule for 16 weeks. Primary outcome parameters were the overall rate and time to relapse with heavy drinking. Secondary outcome parameters were time to the first drink, craving, adherence, tolerability, and safety data (mean corpuscular volume, serum alanine aminotransferase, serum aspartate aminotransferase, γ-glutamyltransferase). RESULTS: The rate of relapse and the time to relapse did not differ significantly between both groups, but less patients treated with LEV terminated treatment early compared with patients receiving placebo. Tolerability and safety data were similar in the LEV group compared with placebo. CONCLUSIONS: Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence.

Efficacy and safety of pregabalin in the treatment of alcohol withdrawal syndrome: a randomized placebo-controlled trial.

AIMS: The objective of this study was to collect preliminary data on the efficacy and safety of pregabalin in attenuating the severity of alcohol withdrawal symptoms during detoxification treatment in alcohol dependence. METHODS: Forty-two alcohol-dependent patients with an alcohol withdrawal syndrome (AWS) were included in the prospective randomized double-blind placebo-controlled trial during inpatient alcohol detoxification. For 6 days, participants either received pregabalin or placebo according to a fixed dose schedule starting with 300 mg/day. Depending on the score of the AWS Scale (AWSS), diazepam was additionally administered as a rescue medication. The primary endpoint was the total amount of diazepam required from Day 2 to 6 of detoxification treatment in each of the two groups. Secondary outcome variables were the difference in AWSS and Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores between Day 2 and 6, tolerability and safety data, drop-out rates as well as changes in the neuropsychological scales. RESULTS: Pregabalin and placebo were equally safe and well tolerated. However, no statistically significant difference was found comparing the total amount of additional diazepam medication required in the two study groups. Pregabalin and placebo also showed similar efficacy according to alterations of scores of the AWSS, CIWA-Ar and neuropsychological scales. The frequency of adverse events and drop-outs did not differ between the both treatment groups. CONCLUSIONS: The study demonstrates the relative safety of pregabalin in the treatment of AWS. However, the results do not provide evidence in favor of pregabalin compared with placebo concerning its efficacy in the treatment of AWS.