The use of LNG-IUS-19.5 mg in daily gynecological routine practice in Germany: data from the Kyleena™ Satisfaction Study (KYSS).

PURPOSE: The Kyleena™ Satisfaction Study (KYSS) provided the first data on 19.5 mg levonorgestrel-releasing intrauterine system (LNG-IUS-19.5 mg) use in routine clinical practice. Here we report results from the German participants in KYSS. METHODS: This prospective, observational, single-arm cohort study recruited women who independently chose to use LNG-IUS-19.5 mg during routine counseling in Germany. Overall satisfaction and bleeding profile satisfaction, continuation rates, and safety profile were evaluated at 12 months or premature end of observation (EoO). RESULTS: In the German study population, LNG-IUS-19.5 mg placement was attempted in 508 women and successful in 506 women. Mean age was 32.3 years, and 60.0% (n = 305/508) were parous. Placement was considered easy and associated with no more than mild pain, even in younger and nulliparous participants. Of those with satisfaction data available, 87.6% (n = 388/443) were satisfied with LNG-IUS-19.5 mg at 12 months/EoO. Satisfaction was similar for parous (86.9%, n = 238/274) and nulliparous (88.8%, n = 150/169) women, and was independent of age, prior contraceptive method, or reason for choosing LNG-IUS-19.5 mg. Most participants (73.6%, n = 299/406) were also satisfied with their bleeding profile at 12 months/EoO, independent of parity, age, prior contraceptive method, presence of amenorrhea or dysmenorrhea severity. The 12-month continuation rate was 84.1% (n = 427/508). Most discontinuations were due to loss to follow-up (8.5%, n = 43/508) or treatment-emergent adverse events (TEAEs) (4.7%, n = 24/508). TEAEs were reported in 12.6% (n = 64) of participants, with 9.3% (n = 47) considered to have an LNG-IUS-19.5 mg-related TEAE. CONCLUSION: Our real-world findings on LNG-IUS-19.5 mg use in German KYSS participants reflected its suitability for a broad population, including young and nulliparous women. CLINICAL TRIAL REGISTRATION: NCT03182140 (date of registration: June 2017).

Does semantic redundancy gain result from multiple semantic priming?

Fiedler, Schröter, and Ulrich (2013) reported faster responses to a single written word when the semantic content of this word (e.g., "elephant") matched both targets (e.g., "animal", "gray") as compared to a single target (e.g., "animal", "brown"). This semantic redundancy gain was explained by statistical facilitation due to a race of independent memory retrieval processes. The present experiment addresses one alternative explanation, namely that semantic redundancy gain results from multiple pre-activation of words that match both targets. In different blocks of trials, participants performed a redundant-targets task and a lexical decision task. The targets of the redundant-targets task served as primes in the lexical decision task. Replicating the findings of Fiedler et al., a semantic redundancy gain was observed in the redundant-targets task. Crucially, however, there was no evidence of a multiple semantic priming effect in the lexical decision task. This result suggests that semantic redundancy gain cannot be explained by multiple pre-activation of words that match both targets.

Illumination frame of reference in the object-reviewing paradigm: A case of luminance and lightness.

The present study combines the object-reviewing paradigm (Kahneman, Treisman, & Gibbs, 1992) with the checkershadow illusion (Adelson, 1995) to contrast the effects of objects' luminance versus lightness on the object-specific preview benefit. To this end, we manipulated objects' luminance and the amount of illumination given by an informative background scene in experiments. In line with previous studies (Moore, Stephens, & Hein, 2010), there was no object-specific preview benefit when objects were presented on a uniformly colored background and luminance switched between objects. In contrast, when objects were presented on the checkershadow illusion background which provided an explanation for the luminance switch, a reliable object-specific preview benefit was observed. This suggests that object correspondence as measured by the object-reviewing paradigm can be influenced by scene-induced, perceived lightness of objects' surfaces. We replicated this finding and moreover showed that the scene context only influences the object-specific preview benefit if the objects are perceived as part of the background scene.

Redundancy gain for semantic features.

In a go/no-go experiment, semantic redundancy gain was assessed for responses to single written words. Specifically, we asked participants to respond only to words whose meaning matched at least one semantic target feature-that is, the target category (e.g., animal), the target color (e.g., gray), or both. On redundant-target trials, the word (e.g., elephant) matched both semantic target features (i.e., gray and animal). On single-target trials, the word (e.g., beaver) matched one target feature (i.e., animal) and a nontarget feature (i.e., brown). We observed shorter reaction times in the redundant-target condition than in the faster single-target condition. Hence, the present study provides the first evidence that redundancy gain is not limited to responses to redundant proximal stimulus features but can also be observed for responses to semantic feature information.

Illusory double flashes can speed up responses like physical ones: evidence from the sound-induced flash illusion.

When a single brief flash is accompanied by two auditory beeps, participants often report perceiving two flashes. The present experiment examined whether the perception of illusory redundant flashes can result in faster responses as compared to the perception of a single flash, because previous research has shown such a redundancy gain for physical stimuli. To this end, participants were asked to respond as rapidly as possible to the onset of any flash. Following their response, they additionally indicated whether they perceived a single flash or a double flash. Most importantly, we observed significant shorter reaction times in response to redundant flashes, irrespective of whether they were physically presented or illusorily perceived. Taken together, our results suggest that an illusory percept can affect simple reaction time in much the same manner as the corresponding physical stimulation.

Fusion prevents the redundant signals effect: evidence from stereoscopically presented stimuli.

In a simple reaction time (RT) experiment, visual stimuli were stereoscopically presented either to one eye (single stimulation) or to both eyes (redundant stimulation), with brightness matched for single and redundant stimulations. Redundant stimulation resulted in two separate percepts when noncorresponding retinal areas were stimulated, whereas it resulted in a single fused percept when corresponding areas were stimulated. With stimulation of noncorresponding areas, mean RT was shorter to redundant than to single stimulation, replicating the redundant signals effect (RSE) commonly found with visual stimuli. With stimulation of corresponding areas, however, no RSE was observed. This suggests that the RSE is driven by the number of percepts rather than by the number of stimulated receptors or sensory organs. These results are consistent with previous findings in the auditory modality and have implications for models of the RSE.

Remodelling of human hamstring autografts after anterior cruciate ligament reconstruction.

PURPOSE: Histological analysis of the remodelling process of human hamstring tendon (HT) grafts after standardized anterior cruciate ligament reconstruction (ACLR) with an accelerated rehabilitation protocol. METHODS: Sixty-seven patients underwent retrieval of mid-substance biopsies after clinically successful hamstring autograft ACLR. Samples were allocated to one of three groups depending on the time point of retrieval: group 1 (6-12 months; n = 15), group 2 (13-24 months; n = 16) and group 3 (>24 months; n = 11). Biopsies from native HT (n = 17) and ACL (n = 8) served as controls. Cellular density, vascular density and myofibroblast density and collagen fibril alignment were analysed by haematoxylin-eosin, Masson-Goldner-Trichrom and immunohistochemical staining protocols. RESULTS: Compared with native HT (330.4/mm²), total cell number was increased in groups 1-3 (Group 1 = 482.0/mm² (P = 0.036); group 2 = 850.9/mm² (P = 0.005); and group 3 = 595.6/mm² (P = 0.043). There were no significant differences between the groups for vessel density. Myofibroblast density was higher in group 2 (199.6/mm²) compared with native HT (1.9/mm², P = 0.014). Collagen orientation was irregular up to 12 months. Thereafter, collagen orientation became more regular, adapting to, but not fully restoring, the appearance of the intact ACL. For the first 12 months, cells were predominantly ovoid. Ensuing cell morphology changed to spindle shaped in group 2 and predominantly narrow long cells over 24 months. CONCLUSION: Human hamstring grafts showed typical stages of graft remodelling, which was not complete up to 2 years after ACLR. The remodelling process in humans was prolonged compared with the results obtained in several animal studies. LEVEL OF EVIDENCE: Case-control study, Level III.

The influence of dichotical fusion on the redundant signals effect, localization performance, and the mismatch negativity.

In two experiments, each including a simple reaction time (RT) task, a localization task, and a passive oddball paradigm, the physical similarity between two dichotically presented auditory stimuli was manipulated. In both experiments, a redundant signals effect (RSE), high localization performance, and a reliable mismatch negativity (MMN) was observed for largely differing stimuli, suggesting that these are coded separately in auditory memory. In contrast, no RSE and a localization rate close to chance level (experiment 1) or at chance (experiment 2) were observed for stimuli differing to a lesser degree. Crucially, for such stimuli a small (experiment 1) or no (experiment 2) MMN were observed. These MMN results indicate that such stimuli tend to fuse into a single percept and that this fusion occurs rather early within information processing.

Temporal attention shortens perceptual latency: a temporal prior entry effect.

The prior entry hypothesis of attention holds that attended stimuli are perceived earlier than unattended stimuli. Whereas this speeding of perceptual processing has been repeatedly demonstrated for spatial attention, it has not been reported within the temporal domain. To fill this gap, we tested whether temporal attention accelerates auditory perceptual processing by employing event-related potentials as on-line indicators of perceptual processing. In a modified oddball paradigm, we presented a single tone in each trial, either a frequent standard tone or an infrequent deviant or target tone. Temporal attention to tones was manipulated via constant foreperiods. We observed that the latency of the N2, an event-related potential reflecting perceptual processing, is shortened by temporal attention. This result provides first evidence for the idea that temporal attention accelerates perceptual processing as suggested by the prior entry hypothesis.

Coactive processing of dimensionally redundant targets within the auditory modality?

Previous reaction time studies have demonstrated coactivation processes within the visual modality for redundant stimuli that differ in two dimensions (e.g., shape and color). The present study provides novel results of analogous processes within the auditory modality. A redundant-target effect (RTE) was obtained in a Go/NoGo experiment using tones that differed in location and/or frequency. Participants were asked to respond to a specific tone location (e.g., left) and/or tone frequency (e.g., 200 Hz) of auditory stimuli. For redundant targets (e.g., a 200 Hz tone presented to the left), an RTE was observed which was too large to be explained by mere statistical facilitation. Therefore, responses to redundant targets were triggered by a combined activation of the target dimensions. The results are consistent with the modular hybrid account of Mordkoff and Yantis (1993).

The effect of antenatal steroid treatment on fetal autonomic heart rate regulation revealed by fetal magnetocardiography (fMCG).

BACKGROUND: Steroid administration to accelerate fetal lung maturation reduces neonatal morbidity and mortality in the case of preterm delivery. Behavioral observations suggest effects on fetal cardiovascular regulation. AIM: We hypothesize that beat to beat heart rate variability (fHRV) derived from fetal magnetocardiography (fMCG) will reveal a direct, acute steroidal effect on fetal autonomic heart rate regulation. SUBJECTS: Eight patients between 29 and 34 weeks of gestation at risk for preterm birth who were treated with betamethasone (2x12 mg within 24 h). STUDY DESIGN: Subjects were studied prior to the first and within 6 h after the second administration. Continuous fMCG was recorded with a 31-channel-SQUID biomagnetometer. Each dataset was processed by subtracting maternal cardiac artefacts and determining the time instants of the fetal heart beats. fHRV analysis was applied to periods of fetal quiescence of 4 min length. OUTCOME MEASURES: We compared fHRV prior versus post steroid administration. RESULTS: Steroid exposure reduced all parameters of overall fHRV significantly. The fHRV parameters representing short term variability remained unaffected. Mean fetal heart rate significantly decreased. The complexity of the heart rate patterns increased. CONCLUSION: Our results suggest an acute shift in the sympatho-vagal balance of fetuses exposed to betamethasone in utero toward sympathetic suppression.

Chondroitin sulfate proteoglycan-based extracellular matrix in chicken (Gallus domesticus) brain.

A specialised form of extracellular matrix consisting of large aggregating chondroitin sulphate proteoglycans connected to hyaluronan and tenascins, as main components, is termed perineuronal nets. These perineuronal nets surround subpopulations of neurons in many vertebrates including man. In this study we investigated the distribution and the postnatal development of perineuronal nets in the brain of the domestic chicken using immunohistochemical, lectin-histochemical and biochemical methods. Perineuronal nets could be identified very early, already on the first postnatal day throughout various regions and nuclei in chicken fore- and midbrains, most expressively in nidopallium, hyperpallium, lateral striatum, globus pallidus and mesopallium. These mostly delicate, scanty structures around the cell bodies of neurons thicken and complete during the first 2 weeks, however, differ in shape and clearness of contours from the mature form of perineuronal nets found in the adult, 3 year old animals. Perineuronal nets frequently co-localized with the potassium channel subunit Kv3.1b characteristic for fast spiking neurons but remained unrevealed around cholinergic or monoaminergic neurons. The early appearance of perineuronal nets in the precocial birds' brain is probably due to the rapid establishment of neuronal morphology and function which is required for the immediate functional and behavioural performance of chicken.

No evidence for a late locus of task switch effects.

When participants are asked to switch from one task to another, reaction time is longer than in task repetition trials. Current models assume that switch costs are located either at the perceptual stage or at the response selection stage. Contrary to this assumption, Hsieh and Liu ([2005. The nature of switch cost: task set configuration or carry-over effect? Cogn. Brain Res. 22,165-175]) found that task switching affects the response-locked lateralized readiness potential and thus provided evidence for a motor locus of switch costs. We hypothesized that this finding may have been due to methodological artefacts. In order to test this hypothesis, we replicated the experiment by Hsieh and Liu (2005) but avoided some potential methodological artefacts of their study. Our results showed a clear effect of task switching on the stimulus-locked lateralized readiness potential but no effect on the response-locked lateralized readiness potential. Thus, the present study questions the evidence for a late, motor locus of task switch effects but rather indicates a locus at the response selection stage.

Human fetal heart rate variability-characteristics of autonomic regulation in the third trimester of gestation.

AIM: To describe developmental aspects of the sympatho-vagal heart rate regulation in the human fetus by applying numerics to visual descriptions of fetal heart rate patterns throughout the third trimester of pregnancy. The focus is to determine potential benefits of this alternative means of assessing the maturation of the fetal autonomic nervous system by analysis of fetal heart rate variability (fHRV). SUBJECTS AND METHODS: The magnetocardiograms of 103 normal fetuses between 24+1 and 41+6 weeks of gestation were studied. Fetal heart beat intervals were determined with a temporal precision of 1 ms. The levels of fetal activity were estimated according to characteristic heart rate patterns (I-III) prior to 32, between 32-35 and beyond 35 (groups 1-3) completed weeks. Mean heart rate (mHR), standard deviation of normal-to-normal beat intervals (SDNN) and root mean square of successive differences of normal beats (RMSSD) served as fHRV indices, mean permutation entropy (PE_Mean) as complexity measure. SDNN/RMSSD was introduced as a potential marker for sympatho-vagal balance. RESULTS: Low activity fHRP (I) were characterized by significantly lower level fHRV indices and higher PE_Mean when compared to fHRP II. We found that SDNN/RMSSD decreases with gestation in fHRP I, which suggests increasing vagal influence. In fHRP III (assigned to active awake fetuses only after 32 weeks), highest level SDNN and mHR are associated with a dramatically reduced complexity. fHRV indices cluster characteristically with the activity levels. CONCLUSIONS: We conclude that a combined analysis of fHRV, based on SDNN/RMSSD and PE_Mean, and fHRP is advantageous in the assessment of maturation of the fetal autonomic nervous system.

Fetal heart rate variability in growth restricted fetuses.

Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.