Ordinal patterns in epileptic brains: Analysis of intracranial EEG and simultaneous EEG-fMRI

Epileptic seizures are associated with high behavioral stereotypy of the patients. In the EEG of epilepsy patients characteristic signal patterns can be found during and between seizures. Here we use ordinal patterns to analyze EEGs of epilepsy patients and quantify the degree of signal determinism. Besides relative signal redundancy and the fraction of forbidden patterns we introduce the fraction of under-represented patterns as a new measure. Using the logistic map, parameter scans are performed to explore the sensitivity of the measures to signal determinism. Thereafter, application is made to two types of EEGs recorded in two epilepsy patients. Intracranial EEG shows pronounced determinism peaks during seizures. Finally, we demonstrate that ordinal patterns may be useful for improving analysis of non-invasive simultaneous EEG-fMRI.

The basel cocktail for simultaneous phenotyping of human cytochrome P450 isoforms in plasma, saliva and dried blood spots.

BACKGROUND AND OBJECTIVE Phenotyping cocktails use a combination of cytochrome P450 (CYP)-specific probe drugs to simultaneously assess the activity of different CYP isoforms. To improve the clinical applicability of CYP phenotyping, the main objectives of this study were to develop a new cocktail based on probe drugs that are widely used in clinical practice and to test whether alternative sampling methods such as collection of dried blood spots (DBS) or saliva could be used to simplify the sampling process. METHODS In a randomized crossover study, a new combination of commercially available probe drugs (the Basel cocktail) was tested for simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Sixteen subjects received low doses of caffeine, efavirenz, losartan, omeprazole, metoprolol and midazolam in different combinations. All subjects were genotyped, and full pharmacokinetic profiles of the probe drugs and their main metabolites were determined in plasma, dried blood spots and saliva samples. RESULTS The Basel cocktail was well tolerated, and bioequivalence tests showed no evidence of mutual interactions between the probe drugs. In plasma, single timepoint metabolic ratios at 2 h (for CYP2C19 and CYP3A4) or at 8 h (for the other isoforms) after dosing showed high correlations with corresponding area under the concentration-time curve (AUC) ratios (AUC0-24h parent/AUC0-24h metabolite) and are proposed as simple phenotyping metrics. Metabolic ratios in dried blood spots (for CYP1A2 and CYP2C19) or in saliva samples (for CYP1A2) were comparable to plasma ratios and offer the option of minimally invasive or non-invasive phenotyping of these isoforms. CONCLUSIONS This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms.

The quiet eye and tasks demands: Do tougher shots need a quieter eye?

The Quiet Eye (QE; Vickers 1996) has been shown to underpin successful performance, differentiating both expertise (inter-individual) and proficiency (intra-individual), with experts and successful attempts characterised by longer QE durations. The QE is proposed to reflect the time needed to organise and fine tune the parameters of movement (e.g. force and direction). In order to examine this prediction and build upon previous research we experimentally manipulated the difficulty of a golf putting task; we hypothesised that if the QE is related to motor programming then a more difficult task should be associated with longer QE durations. 33 golfers (M age= 21.16, SD= 3.98) with an average handicap of 6.5 (SD= 6.02) performed putts in 4 conditions of increasing difficulty. We manipulated the length of the golf putt (short-4ft, long-8ft) and the contact point of the putter head (large-1.7cm, small-0.5cm,) giving increasingly difficult putting conditions of short-large [1], short-small [2], long-large [3] and long-small [4]. We measured performance (radial error from hole in cm) and QE (in ms) for 10 putts in each condition. A repeated measures ANOVA was performed on the performance and QE data. The performance data suggest that we were successful in increasing the difficulty of the task (F (3,93) = 26.46. p = .000), with the best performance in condition [1] (8.57cm), followed by [2] (9.10cm) followed by [3] (16.11cm) and finally the worst performance was in condition [4] (23.40cm). The QE data suggest that, in keeping with our hypothesis, the QE was lengthened as task difficulty increased (F (3,87) = 11.91, p = .043). The QE was shortest in condition [1] (1787.85ms) and increased to condition [2] (1939.78ms) and condition [3] (2076.51ms), with the longest QE in condition [4] (2164.08ms). More detailed analysis of the QE reveal that it was the proportion of the QE that occurred before movement initiation (pre-QE) which increased with shot difficulty, rather than the proportion that occurred during the swing (Online-QE; see Vine et al., 2013). Results support the notion that more complex tasks are associated with a longer QE duration, specifically participants appear to spend longer fixating the target prior to movement. This likely reflects the time needed to process visual information gathered in a pre-performance routine, to inhibit external distraction, and to pre-programme the increasingly difficult parameters of the movement. Vickers, J.N. (1996). Visual control when aiming at a far target. Journal of Experimental Psychology: Human Perception and Performance, 22, 342-354. Vine, S.J. et al. (2013). Quiet eye and choking: Online control breaks down at the point of performance failure. Medicine and Science in Sports and Exercise, 45, 1988-1994.

Pile-dwellings of the Neolithic and the Bronze Age in Switzerland. Long-term research and future tasks

Swiss lake-side settlements dating between 4300 and 800 BC were first recognized in the early 19th century and between 1854 and 1880 early research boomed due to the first scientific studies and the artificial lowering of lakes in Western Switzerland. In the 20th century underwater and wetland archaeology experienced an enormous surge not only because of large rescue excavations, due to extensive motorway construction projects but also due to the evolution of modern IT technology in the 1970s. For the first time huge quantities of ancient wooden structures could be dated by dendrochronology. This produced a quantum leap in the 150 years of pile-dwelling research. In 2011, the UNESCO World Heritage Committee recognized the outstanding universal value of these sites. This article presents an overview about Swiss pile-dwellings of the Neolithic and the Bronze Age and the results of two recent diploma works (case study Sutz-Lattrigen Haupstation innen and case study Seedorf Lobsigensee) as examples of research and cooperation between universities and government agencies for cultural heritage management.

Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).

Prediction and prevention of psychosis: current progress and future tasks

Prevention of psychoses has been intensively investigated within the past two decades, and particularly, prediction has been much advanced. Depending on the applied risk indicators, current criteria are associated with average, yet significantly heterogeneous transition rates of ≥30 % within 3 years, further increasing with longer follow-up periods. Risk stratification offers a promising approach to advance current prediction as it can help to reduce heterogeneity of transition rates and to identify subgroups with specific needs and response patterns, enabling a targeted intervention. It may also be suitable to improve risk enrichment. Current results suggest the future implementation of multi-step risk algorithms combining sensitive risk detection by cognitive basic symptoms (COGDIS) and ultra-high-risk (UHR) criteria with additional individual risk estimation by a prognostic index that relies on further predictors such as additional clinical indicators, functional impairment, neurocognitive deficits, and EEG and structural MRI abnormalities, but also considers resilience factors. Simply combining COGDIS and UHR criteria in a second step of risk stratification produced already a 4-year hazard rate of 0.66. With regard to prevention, two recent meta-analyses demonstrated that preventive measures enable a reduction in 12-month transition rates by 54-56 % with most favorable numbers needed to treat of 9-10. Unfortunately, psychosocial functioning, another important target of preventive efforts, did not improve. However, these results are based on a relatively small number of trials; and more methodologically sound studies and a stronger consideration of individual profiles of clinical needs by modular intervention programs are required

Simultaneous detection and discrimination of virulent and benign Dichelobacter nodosus in sheep of flocks affected by foot rot and in clinically healthy flocks by competitive real-time PCR.

Ovine foot rot caused by Dichelobacter nodosus is affecting sheep worldwide. The current diagnostic methods are difficult and cumbersome. Here, we present a competitive real-time PCR based on allelic discrimination of the protease genes aprV2 and aprB2. This method allows direct detection and differentiation of virulent and benign D. nodosus from interdigital skin swabs in a single test. Clinically affected sheep harbored high loads of only virulent strains, whereas healthy sheep had lower loads of predominantly benign strains.

Retinal Laser Lesion Visibility in Simultaneous Ultra-High Axial Resolution Optical Coherence Tomography

Ex vivo porcine retina laser lesions applied with varying laser power (20 mW–2 W, 10 ms pulse, 196 lesions) are manually evaluated by microscopic and optical coherence tomography (OCT) visibility, as well as in histological sections immediately after the deposition of the laser energy. An optical coherence tomography system with 1.78 um axial resolution specifically developed to image thin retinal layers simultaneously to laser therapy is presented, and visibility thresholds of the laser lesions in OCT data and fundus imaging are compared. Optical coherence tomography scans are compared with histological sections to estimate the resolving power for small optical changes in the retinal layers, and real-time time-lapse scans during laser application are shown and analyzed quantitatively. Ultrahigh-resolution OCT inspection features a lesion visibility threshold 40–50 mW (17 reduction) lower than for visual inspection. With the new measurement system, 42 of the lesions that were invisible using state-of-the-art ophthalmoscopic methods could be detected.

Developmental tasks as a framework to study personality development in adulthood and old age

Research consistently shows that personality development is a lifelong phenomenon, with mean-level and rank-order changes occurring in all life phases. What happens during specific life phases that can explain these developmental patterns? In the present paper, we review literature linking personality development in different phases of adulthood to developmental tasks associated with these phases. Building on previous work, we describe several categories of developmental tasks that are present in all phases of adulthood. However, the specific tasks within these categories change across adulthood from establishing new social roles in early adulthood to maintaining them in middle adulthood and preventing losses in old age. This trajectory is reflected in mean-level changes in personality, which indicates development towards greater maturity (increases in social dominance, conscientiousness, and emotional stability) in early and middle adulthood, but less so at the end of life. Importantly, developmental tasks are not only associated with mean-level changes, but the way in which people deal with these tasks is also related to rank-order changes in personality. We provide an outlook for future research on how the influence of historical time on the normativeness of developmental tasks might be reflected in personality development.

Evaluation of a new experimental model to study bone healing after ridge expansion with simultaneous implant placement--a pilot study in minipigs.

OBJECTIVE To evaluate the suitability of a minipig model for the study of bone healing and osseointegration of dental implants following bone splitting and expansion of narrow ridges. MATERIAL AND METHODS In four minipigs, the mandibular premolars and first molars were extracted together with removal of the buccal bone plate. Three months later, ridge splitting and expansion was performed with simultaneous placement of three titanium implants per quadrant. On one side of the mandible, the expanded bone gap between the implants was filled with an alloplastic biphasic calcium phosphate (BCP) material, while the gap on the other side was left unfilled. A barrier membrane was placed in half of the quadrants. After a healing period of 6 weeks, the animals were sacrificed for histological evaluation. RESULTS In all groups, no bone fractures occurred, no implants were lost, all 24 implants were osseointegrated, and the gap created by bone splitting was filled with new bone, irrespective of whether BCP or a barrier membrane was used. Slight exposure of five implants was observed, but did not lead to implant loss. The level of the most coronal bone-to-implant contact varied without being dependent on the use of BCP or a barrier membrane. In all groups, the BCP particles were not present deep in the bone-filled gap. However, BCP particles were seen at the crestal bone margin, where they were partly integrated in the new bone. CONCLUSIONS This new minipig model holds great promise for studying experimental ridge splitting/expansion. However, efforts must be undertaken to reduce implant exposure and buccal bone resorption.

IMRT with ¹⁸FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer

BACKGROUND To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC). METHODS The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control. RESULTS The median number of irradiated LNs per patient was 3 (range: 1-6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis. CONCLUSION IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer.