Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

The revival of the psychedelic experience scale: Revealing its extended-mystical, visual, and distressing experiential spectrum with LSD and psilocybin studies.

BACKGROUND: Research with the Psychedelic Experience Questionnaire/Scale (PES) focuses on questions relating to mystical experience (Mystical Experience Questionnaire (MEQ)). The psychometric potential of the non-MEQ items of the PES remains largely unexplored. AIMS: We investigated whether the PES also yields subscales besides the MEQ30 subscales. METHODS: Data from 239 PES measurements (140 healthy participants) from six studies with moderate to high doses of lysergic acid diethylamide and/or psilocybin were included. New subscales (with items other than MEQ30) were created and validated as follows: (1) theoretical derivation of candidate items; (2) removal of items with rare experiences; (3) exploratory factor analysis; and (4) confirmatory factor analysis. Correlations of subscales within the PES and between the PES and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) were performed. In addition, a cluster analysis using all items (except rare experiences) was performed. RESULTS: The reliability of the four original factors of the MEQ30 was confirmed and four additional factors for the non-MEQ items were revealed: paradoxicality, connectedness, visual experience, and distressing experience. The first two additional factors were strongly correlated with the MEQ30 mystical subscale. Adding the new subscales to the MEQ30 subscales increased the explained variance with the 5D-ASC. The cluster analysis confirmed our main results and provided additional insights for future psychedelic psychometrics. CONCLUSION: The study yields a new validated 6-factor structure for extended mystical experience (MEQ40: MEQ30 + Paradoxicality + Connectedness) and covers psychedelic experience as a whole more comprehensively than has hitherto been possible within a single questionnaire (PES48). The entire PES (PES100) can also be used for further future psychedelic-psychometric research.

Case report: Maintaining altered states of consciousness over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects: some initial lessons from a personalized-dosing single-case study.

Background: The interest in psychoactive agents for treating mental disorders has gathered a growing body of scientific interest. However, research on the relationship between altered states of consciousness (ASCs) and ketamine's antidepressant properties is still limited. Likewise, approaches to sustain early treatment success for the long-term are needed. Taking both aspects into account, the question arises whether the persistence of recurrent ASCs during the subsequent infusion sessions is crucial for the preservation of antidepressant effects during prolonged continued ketamine therapy. Aim: In this case study we explored whether recurrent ASC experiences across a large number of infusions are associated with improved antidepressant effects in a single case study. Methods: A 62-year-old patient with treatment-resistant depression, who has been suffering from depressive episodes for over 20 years, was observed for 12 consecutive infusions across 16 weeks. ASCs during ketamine sessions were measured with the 5D-ASC, and pre/post-infusion depression scores with the BDI-II questionnaire. To emphasize psychoactive experiences a personalized antidepressant dose regimen was used. Results: We found a strong correlation between the experienced ASCs during ketamine infusions and the antidepressant effect: the stronger the ASCs overall, the stronger the resulting antidepressant effect. This correlation was consistently observed throughout the infusion series, independent of the number of ketamine sessions completed before. However, despite a personalized dose regimen, neither peri-infusion ASCs nor antidepressant effects could be established on a regular basis, leading overall to no improvement in treatment outcome. Conclusion: Maintaining psychoactive effects over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects. However, for some depressed individuals maintenance of antidepressant effects and/or peri-infusion ASCs might not be achieved, even when personalized dosing is used.

CD45RA and CD45RO Are Regulated in a Cell-Type Specific Manner in Inflammation and Sepsis.

CD45 is a transmembrane glycoprotein that is located on the surface of all leukocytes and modulates both innate and adaptive immune system functions. In a recent study, inflammation modulated the CD45 expression in leukocytes, but the effect on the expression of CD45 subtypes is unknown. In the present study, we therefore investigated the effect of inflammatory conditions in humans (surgery, sepsis) and ex vivo incubation with lipopolysaccharides (LPS) on the expression of the subtypes CD45RA and CD45RO in granulocytes, lymphocytes, and monocytes. Whole blood samples were obtained from healthy volunteers, postoperative patients, and patients with sepsis at day 1 of diagnosis, respectively. Samples were incubated with fluorescent antibodies directed against CD45, CD45RA and CD45RO in the absence and presence of lipopolysaccharide and subjected to flow cytometry. In comparison to volunteers, CD45RA surface expression in postoperative and septic patients was reduced by 89% exclusively on granulocytes, but not on lymphocytes or monocytes. In contrast, CD45RO was exclusively reduced on lymphocytes, by 82%, but not on other cell types. Receiver operating characteristic curve analyses demonstrated that CD45RA (on granulocytes) and CD45RO (on lymphocytes) allow a good differentiation of volunteers and patients with sepsis (AUC = 0.9; p = 0.0001). The addition of LPS to the whole blood samples obtained from volunteers, postoperative patients, and septic patients markedly increased the CD45RO expression in granulocytes, lymphocytes, and monocytes. In contrast, LPS reduced CD45RA exclusively on monocytes. In conclusion, the surface expression of CD45RA and CD45RO is regulated in inflammation in a cell-type- and stimulus-specific manner. Considering that CD45 subtypes are critically involved in immune system signaling, the pathophysiologic and diagnostic implications warrant further investigation.

Linking paranormal and conspiracy beliefs to illusory pattern perception through signal detection theory.

Previous research indicates that irrational beliefs (Paranormal beliefs & conspiracy theory endorsement) are associated with the perception of patterns in noise, but the previous findings do not conclusively describe this relationship. This study aims to disentangle the underlying parameters of this association by applying a signal detection theory approach, thus allowing to distinguish illusory pattern perception (false alarms) from perceptual sensitivity and response tendencies-while also taking base rate information into account. Results from a large sample (N = 723) indicate that paranormal beliefs relate to a more liberal response bias and a lower perceptual sensitivity, and that this relationship is driven by illusory pattern perception. Such a clear pattern could not be observed for conspiracy beliefs, for which the increase in false alarm rates was moderated by the base rate. The associations between irrational beliefs and illusory pattern perception were however less substantial compared to other sources of variance. Implications are discussed.

A potential dissociation between perception and production version for bounded but not unbounded number line estimation.

BACKGROUND: What, exactly, do number line estimation (NLE) tasks measure? Different versions of the task were observed to have different effects on performance. METHOD: We investigated associations between the production (indicating the location) and perception version (indicating the number) of the bounded and unbounded NLE task and their relationship to arithmetic. RESULTS: A stronger correlation was observed between the production and perception version of the unbounded than the bounded NLE task, indicating that both versions of the unbounded-but not the bounded-NLE task measure the same construct. Moreover, overall low but significant associations between NLE performance and arithmetic were only observed for the production version of the bounded NLE task. CONCLUSION: These results substantiate that the production version of bounded NLE seems to rely on proportion judgment strategies, whereas both unbounded versions and the perception version of the bounded NLE task may rely more on magnitude estimation.

Illusory perception of visual patterns in pure noise is associated with COVID-19 conspiracy beliefs.

Just as perceptual heuristics can lead to visual illusions, cognitive heuristics can lead to biased judgements, such as "illusory pattern perception" (i.e., seeing patterns in unrelated events). Here we further investigated the common underlying mechanism behind irrational beliefs and illusory pattern perception in visual images. For trials in which no object was present in the noise, we found that the tendency to report seeing an object was positively correlated with the endorsement of both COVID-19 specific conspiracy theories and paranormal beliefs. The present results suggest that the cognitive bias to see meaningful connections in noise can have an impact on socio-political cognition as well as on perceptual decision making.

Acceptance and Adherence to COVID-19 Preventive Measures are Shaped Predominantly by Conspiracy Beliefs, Mistrust in Science and Fear - A Comparison of More than 20 Psychological Variables.

The global coronavirus (COVID-19) pandemic sparked a great interest in psychological factors that determine or explain peoples' responses to the novel threatening situation and the preventive measures (e.g. wearing masks, social distancing). In this study, we focused on contaminated mindware (conspiracy and paranormal beliefs) and investigated its relationship with both acceptance of and adherence to COVID-19 preventive measures, along with other variables from the domains of emotion (trait anxiety, fear), traditional personality traits (Big 5, locus of control, optimism/pessimism) and motivation (self-control, dispositional regulatory focus). A total of 22 variables were measured in an online survey (N = 374) that took place during the second wave of COVID-19 (Nov. 2020 - March 2021) in Switzerland. Of all variables, the endorsement of specific COVID-19 conspiracy beliefs was most strongly associated with lower acceptance and adherence to the preventive measures, together with mistrust in science and a more right-wing political orientation. In contrast, fear of COVID-19 and prevention regulatory focus were positively associated with acceptance and adherence. Our results therefore highlight the importance of fighting (conspiratorial) misinformation and of increasing the perceived credibility of science in reducing the spread of the coronavirus. Moreover, when acceptance was used as predictor for adherence, agreeableness and dispositional prevention regulatory focus still explained unique variance in adherence, suggesting that such personality and motivational variables play an important role in adhering and regulating preventive behaviour independent from the attitude towards the preventive measures themselves.

Happiness feels light and sadness feels heavy: introducing valence-related bodily sensation maps of emotions.

Bodily sensation mapping (BSM) is a recently developed self-report tool for the assessment of emotions in which people draw their sensations of activation in a body silhouette. Following the circumplex model of affect, activity and valence are the underling dimensions of every emotional experience. The aim of this study was to introduce the neglected valence dimension in BSM. We found that participants systematically report valence-related sensations of bodily lightness for positive emotions (happiness, love, pride), and sensations of bodily heaviness in response to negative emotions (e.g., anger, fear, sadness, depression) with specific body topography (Experiment 1). Further experiments showed that both computers (using a machine learning approach) and humans recognize emotions better when classification is based on the combined activity- and valence-related BSMs compared to either type of BSM alone (Experiments 2 and 3), suggesting that both types of bodily sensations reflect distinct parts of emotion knowledge. Importantly, participants found it clearer to indicate their bodily sensations induced by sadness and depression in terms of bodily weight than bodily activity (Experiment 2 and 4), suggesting that the added value of valence-related BSMs is particularly relevant for the assessment of emotions at the negative end of the valence spectrum.

Summing up: A functional role of eye movements along the mental number line for arithmetic.

In Western cultures, small-left and large-right spatial-numerical associations are constantly found in various simple number processing tasks. It has recently been suggested that spatial associations are also involved in more complex number processing, for example that individuals make rightward or upward "mental" movements along the number line during addition, and leftward or downward movements during subtraction. In line with this, it has been shown that participants' spontaneous eye movements on a blank screen during upward and downward counting follow such associations. The present research investigated whether eye movements along the number line are simply an epiphenomenon of the recruitment of a spatial reference frame, or whether they play a functional role for the arithmetic computation. This question was addressed by using multi-step problems (e.g., 59 + 5 + 4 + 3) that show a larger proportion of computation (vs. retrieval) when compared to single-step problems (e.g., 59 + 5), as confirmed in Pretest 1. Moreover, the question was addressed only for addition problems and vertical eye movements, because spatial-arithmetic associations were not found in the other conditions (subtraction, horizontal eye movements) in Pretest 2. In the main experiment, participants (n = 29) solved addition problems while following a moving dot with their eyes (smooth pursuit) either in a congruent (upward) or incongruent (downward) direction, or while keeping their eyes fixated on to the center of the screen, or while moving their eyes freely on a blank screen. Arithmetic performance was faster in the congruent condition (upward eye movements) when compared to the other conditions (downward eye movements, central fixation, free viewing). These results suggest that vertical shifts in spatial attention along the mental number line are functionally involved in addition. The results support the view of shared mechanisms for directing spatial attention in external (visual) and representational (number space). Implications for embodied views of number processing are discussed.

A Multigene Phylogeny of Native American Hawkweeds (Hieracium Subgen. Chionoracium, Cichorieae, Asteraceae): Origin, Speciation Patterns, and Migration Routes.

Native American hawkweeds are mainly mountainous species that are distributed all over the New World. They are severely understudied with respect to their origin, colonization of the vast distribution area, and species relationships. Here, we attempt to reconstruct the evolutionary history of the group by applying seven molecular markers (plastid, nuclear ribosomal and low-copy genes). Phylogenetic analyses revealed that Chionoracium is a subgenus of the mainly Eurasian genus Hieracium, which originated from eastern European hawkweeds about 1.58-2.24 million years ago. Plastid DNA suggested a single origin of all Chionoracium species. They colonized the New World via Beringia and formed several distinct lineages in North America. Via one Central American lineage, the group colonized South America and radiated into more than a hundred species within about 0.8 million years, long after the closure of the Isthmus of Panama and the most recent uplift of the Andes. Despite some incongruences shown by different markers, most of them revealed the same crown groups of closely related taxa, which were, however, largely in conflict with traditional sectional classifications. We provide a basic framework for further elucidation of speciation patterns. A thorough taxonomic revision of Hieracium subgen. Chionoracium is recommended.

Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study.

Background: Cognition that is not dominated by thinking in terms of opposites (opposite diminishing) or by making judgments (non-judging) can be found both in Buddhist/mindfulness contexts and in mental states that are fostered by dissociative psychedelics (N-methyl-D-aspartate antagonists) such as ketamine. Especially for the Buddhist/mindfulness case, both opposite diminishing and non-judging have been proposed to relate to mental well-being. Whether ketamine-occasioned opposite diminishing and/or non-judging relate to increased mental well-being in the form of antidepressant response is unknown, and was investigated in the present study. Methods: In this open-label outpatient study, the dose level and frequency for the ketamine infusions were adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits-a novel dose regimen that we term personalized antidepressant dosing. In general, treatment started with an initial series of ketamine infusions with a dosage of 0.5 mg/kg body weight and was then adjusted (usually increased). A possible relationship between ketamine-induced antidepressant benefits and retrospectively reported peri-infusion experiences of opposite diminishing and non-judging was assessed based on a total of 45 ketamine-infusion treatment sessions from 11 different patients suffering from depression. Opposite diminishing and non-judging were measured with the two items from the Altered States of Consciousness Inventory (ASCI) that measure these concepts. Depression was measured with the Beck Depression Inventory (BDI-II). Results: Peri-infusion experiences of both opposite diminishing and non-judging were associated with antidepressant responses confirming our hypothesis. Furthermore, opposite diminishing and non-judging were closely related to one another while relating to antidepressant response in distinguishable ways. Conclusion: Future controlled randomized trials with dissociative and other psychedelics and with a larger number of participants are needed to establish the possible link of psychedelically induced opposite diminishing and non-judging with an antidepressant response more firmly.

Elevated Pre- and Postoperative ROTEM™ Clot Lysis Indices Indicate Reduced Clot Retraction and Increased Mortality in Patients Undergoing Liver Transplantation.

Background: The ROTEM™ clot lysis index, describing the decrease in firmness of a clot with time, predicts mortality in various settings. The variability of the clot lysis index in surgical procedures and the involved pathophysiological mechanisms are unknown. We therefore compared pre- and postoperative clot lysis indices in liver transplantation (LTX) procedures, determined the eventual association with mortality, and investigated the mechanisms underlying decreased clot lysis index using inhibitors of fibrinolysis and clot retraction, respectively. Methods: In this retrospective cohort study, data on pre- and post-transplant ROTEM™ findings as obtained with EXTEM (tissue factor activation), INTEM (intrinsic system activation), FIBTEM (extrinsic system activation and inhibition of clot retraction), APTEM (extrinsic system activation and fibrinolysis inhibition), conventional laboratory coagulation tests, blood loss, transfusion of blood products, and outcome were registered. Results: Pre-transplant clot lysis indices showed a broad distribution ranging from 75% to 99% independent of the activator used (EXTEM, INTEM). During the surgical procedure, median clot lysis index values markedly increased from 92% to 97% (EXTEM) and 93% to 98% (INTEM), respectively (p < 0.0001 each). Aprotinin had no effect on either pre- or postsurgical clot lysis indices. Inhibition of platelet clot retraction with cytochalasin D (FIBTEM) markedly increased the preoperative clot lysis index. High pre- and post-transplantation clot lysis indices were associated with increased mortality irrespective of the activator used (EXTEM, INTEM) and the inhibition of fibrinolysis (APTEM). Inhibition of clot retraction (FIBTEM) abolished the association of clot lysis index with mortality in both pre- and post-transplantation samples. Conclusion: Both pre- and postoperative ROTEM™ clot lysis indices predict mortality in patients following liver transplantation. Inhibitor experiments reveal that the clot lysis index is not an indicator of fibrinolysis, but indicates platelet clot retraction. The marked increase of clot lysis index during liver transplantation is caused by a decrease in clot retraction with eventual consequences for clot stability, retraction of wound margins, and reperfusion of vessels in case of thrombosis.

The Edge of Unknown: Postoperative Critical Care in Liver Transplantation.

Perioperative care of patients undergoing liver transplantation (LT) is very complex. Metabolic derangements, hypothermia, coagulopathy and thromboses, severe infections, and graft dysfunction can affect outcomes. In this manuscript, we discuss several perioperative problems that can be encountered in LT recipients. The authors present the most up-to-date information regarding predicting and treating hemodynamic instability, coagulation monitoring and management, postoperative ventilation strategies and early extubation, management of infections, and ESLD-related pulmonary complications. In addition, early post-transplant allograft dysfunction will be discussed.

Differential Regulation of CD45 Expression on Granulocytes, Lymphocytes, and Monocytes in COVID-19.

CD45 is a transmembrane glycoprotein and protein tyrosine phosphatase expressed on the surface of all nucleated hematopoietic cells. While there is increasing evidence demonstrating the involvement of CD45 in immune system regulation, no information on CD45 expression in inflammation and sepsis is currently available. Therefore, we determined the CD45 surface expression on granulocytes, lymphocytes, and monocytes in patients with COVID-19 and healthy volunteers in both absence and presence of lipopolysaccharide (LPS). Following approval by the local ethics committee, whole blood samples were obtained from patients with COVID-19 infection on day 1 of hospital admission and healthy volunteers. Samples were incubated in absence and presence of LPS and CD45 was measured in granulocytes, lymphocytes, and monocytes using flow cytometry. In comparison with healthy individuals, COVID-19 patients showed an increased CD45 expression on the surface of granulocytes (+35%, p < 0.02) and lymphocytes (+39%, p < 0.0001), but a reduced CD45 expression on monocytes (−35%, p < 0.0001). LPS incubation of whole blood from healthy individuals increased the CD45 expression on granulocytes (+430%, p < 0.0001), lymphocytes (+32%, p = 0.0012), and monocytes (+36%, p = 0.0005), respectively. LPS incubation of whole blood samples from COVID-19 patients increased the CD45 expression on granulocytes and monocytes, and decreased the CD45 expression on lymphocytes. In conclusion, CD45 expression on leucocytes is altered: (1) in COVID-19 patients, and (2) in in vitro endotoxemia in a complex cell-specific way, thus representing a new immunoregulatory mechanism.

Retrospective evaluation of a robust hybrid planning technique established for irradiation of breast cancer patients with included mammary internal lymph nodes.

BACKGROUND: The irradiation of breast cancer patients with included internal mammary lymph nodes challenges radiation planning with regard to robustness and protection of OARs. In this publication, a feasible hybrid radiation technique is presented with a retrospective dosimetric and radiobiological analysis of patient data of our institute from 2016 to 2020 and robustness analysis. METHODS: The proposed hybrid irradiation technique consists of two IMRT tangents and two partial VMAT fields. The retrospective dosimetric and radiobiological evaluation are made for 217 patient treatments (right- and left-sided). The robustness is evaluated regarding an artificial swelling from 0.4 to 1.5 cm for a random example patient and compared to a pure VMAT planning technique with use of a virtual bolus. The out of field stray dose is calculated for a selected patient plan and compared to alternative radiation techniques. RESULTS: The coverage D95% of the PTVEval (with breast swelling of 1.5 cm) changes for the hybrid plan from 96.1 to 92.1% of prescribed dose and for the pure VMAT plan from 94.3 to 87%. The retrospective dosimetric evaluation of patient irradiations reveals a Dmean for total lung 6.5 ± 0.9 Gy (NTCP[Semenenko 2008] 2.8 ± 0.5%), ipsilateral lung 10.9 ± 1.5 Gy, contralateral lung 2.2 ± 0.6 Gy, heart 2.1 ± 1.1 Gy (ERR[Schneider 2017] 0.02 ± 0.17%) and contralateral breast 1.7 ± 0.6 Gy. The scatter dose of the hybrid irradiation technique is higher than for pure VMAT and lower than for pure IMRT irradiation. CONCLUSIONS: The feasibility of the proposed planning technique is shown by treating many patients with this technique at our radiotherapy department. The hybrid radiation technique shows a good sparing of the OARs in the retrospective analysis and is robust with regards to a breast swelling of up to 1.5 cm. The slightly higher stray dose of the hybrid technique compared to a pure VMAT technique originates from higher number of MUs and lower conformity.

Imagined paralysis reduces motor cortex excitability.

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near-threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment.

Development of whole-body representation and dose calculation in a commercial treatment planning system.

For the epidemiological evaluation of long-term side effects of radiotherapy patients, it is important to know the doses to organs and tissues everywhere in the patient. Computed tomography (CT) images of the patients which contain the anatomical information are sometimes available for each treated patient. However, the available CT scans usually cover only the treated volume of the patient including the target and surrounding anatomy. To overcome this limitation, in this work we describe the development of a software tool using the Varian Eclipse Scripting API for extending a partial-body CT to a whole-body representation in the treatment planning system for dose calculation. The whole-body representation is created by fusing the partial-body CT with a similarly sized whole-body computational phantom selected from a library containing 64 phantoms of different heights, weights, and genders. The out-of-field dose is calculated with analytical models from the literature and merged with the treatment planning system-calculated dose. To test the method, the out-of-field dose distributions on the computational phantoms were compared to dose calculations on whole-body patient CTs. The mean doses, D2% and D98% were compared in 26 organs and tissues for 14 different treatment plans in 5 patients using 3D-CRT, IMRT, VMAT, coplanar and non-coplanar techniques. From these comparisons we found that mean relative differences between organ doses ranged from -10% and +20% with standard deviations of up to 40%. The developed method will help epidemiologists and researchers estimate organ doses outside the treated volume when only limited treatment planning CT information is available.

Early is left and up: Saccadic responses reveal horizontal and vertical spatial associations of serial order in working memory.

Maintaining serial order in working memory is crucial for cognition. Recent theories propose that serial information is achieved by positional coding of items on a spatial frame of reference. In line with this, an early-left and late-right spatial-positional association of response code (SPoARC) effect has been established. Various theoretical accounts have been put forward to explain the SPoARC effect (the mental whiteboard hypothesis, conceptual metaphor theory, polarity correspondence, or the indirect spatial-numerical association effect). Crucially, while all these accounts predict a left-to-right orientation of the SPoARC effect, they make different predictions regarding the direction of a possible vertical SPoARC effect. In this study, we therefore investigated SPoARC effects along the horizontal and vertical spatial dimension by means of saccadic responses. We replicated the left-to-right horizontal SPoARC effect and established for the first time an up-to-down vertical SPoARC effect. The direction of the vertical SPoARC effect was in contrast to that predicted by metaphor theory, polarity correspondence, or by the indirect spatial-numerical association effect. Rather, our results support the mental whiteboard-hypothesis, according to which positions can be flexibly coded on an internal space depending on the task demands. We also found that the strengths of the horizontal and vertical SPoARC effects were correlated, showing that some people are more prone than others to use spatial references for position coding. Our results therefore suggest that context templates used for position marking are not necessarily spatial in nature but depend on individual strategy preferences.

Platelet-Therapeutics to Improve Tissue Regeneration and Wound Healing-Physiological Background and Methods of Preparation.

Besides their function in primary hemostasis, platelets are critically involved in the physiological steps leading to wound healing and tissue repair. For this purpose, platelets have a complex set of receptors allowing the recognition, binding, and manipulation of extracellular structures and the detection of pathogens and tissue damage. Intracellular vesicles contain a huge set of mediators that can be released to the extracellular space to coordinate the action of platelets as other cell types for tissue repair. Therapeutically, the most frequent use of platelets is the intravenous application of platelet concentrates in case of thrombocytopenia or thrombocytopathy. However, there is increasing evidence that the local application of platelet-rich concentrates and platelet-rich fibrin can improve wound healing and tissue repair in various settings in medicine and dentistry. For the therapeutic use of platelets in wound healing, several preparations are available in clinical practice. In the present study we discuss the physiology and the cellular mechanisms of platelets in hemostasis and wound repair, the methods used for the preparation of platelet-rich concentrates and platelet-rich fibrin, and highlight some examples of the therapeutic use in medicine and dentistry.