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Zebrafish (Danio rerio) are a popular model organism in behavioral pharmacology research due to many genetic and neurological similarities with humans. As a social species, the presence (or absence) of conspecifics during housing and testing is likely to affect behavior, but these effects have not yet been well characterized. The goal of the current study was to better understand how social variables influence depth preference in zebrafish. Subjects were housed individually, in pairs, or in groups of four, then tested in a novel tank either individually or with their tankmates. Prior to testing, fish were exposed to 0.0%, 0.5%, or 1.0% ethanol. Behavior was recorded using a combination of manual coding methods and ANYMaze (™) video-tracking. Our results demonstrated more exploration by fish tested with their tankmates, and less exploration by fish tested in isolation. Additionally, the effects of ethanol on diving behavior were modulated by social groups during both housing and testing. We conclude that social variables likely contribute to the variability of behavior often observed in pharmacological research with zebrafish, and that additional effort should be directed to both standardization and further characterization of these variables., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Traveling Salesman Problem (TSP) is an optimization problem in which the subject attempts to find the shortest possible route that passes through a set of fixed locations exactly once. The TSP is used in cognitive and behavioral research to study problem solving and spatial navigation. While the TSP has been studied in some depth from this perspective, the biological mechanisms underlying the behavior have not yet been explored. The hippocampus is a structure in the brain that is known to be involved in tasks that require spatial memory. Because the TSP requires spatial problem solving, we designed the current study to determine whether the hippocampus is required to find efficient solutions to the TSP, and if so, what role the hippocampus serves. Rats were pretrained on the TSP, which involved learning to retrieve bait from targets in a variety of spatial configurations. Matched for performance, rats were then divided into two groups, receiving either a hippocampal lesion or a control sham surgery. After recovering from surgery, the rats were tested on eight new configurations. A variety of behavioral measures were recorded, including distance travelled, number of revisits, memory span, and latency. The results showed that the sham group outperformed the lesion group on most of these measures. Based on the behavioral data and histological tissue analysis of each group, we determined that the hippocampus is involved in successful performance in the TSP, particularly regarding memory for which targets have already been visited., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Infectious complications are the major cause of morbidity and mortality after solid organ and stem cell transplantation. To better understand host and environmental factors associated with an increased risk of infection as well as the effect of infections on function and survival of transplanted organs, we established the DZIF Transplant Cohort, a multicentre prospective cohort study within the organizational structure of the German Center for Infection Research. At time of transplantation, heart-, kidney-, lung-, liver-, pancreas- and hematopoetic stem cell- transplanted patients are enrolled into the study. Follow-up visits are scheduled at 3, 6, 9, 12 months after transplantation, and annually thereafter; extracurricular visits are conducted in case of infectious complications. Comprehensive standard operating procedures, web-based data collection and monitoring tools as well as a state of the art biobanking concept for blood, purified PBMCs, urine, and faeces samples ensure high quality of data and biosample collection. By collecting detailed information on immunosuppressive medication, infectious complications, type of infectious agent and therapy, as well as by providing corresponding biosamples, the cohort will establish the foundation for a broad spectrum of studies in the field of infectious diseases and transplant medicine. By January 2020, baseline data and biosamples of about 1400 patients have been collected. We plan to recruit 3500 patients by 2023, and continue follow-up visits and the documentation of infectious events at least until 2025. Information about the DZIF Transplant Cohort is available at https://www.dzif.de/en/working-group/transplant-cohort .

This study examines the compatibility of multielectrolyte additives for NMC-silicon lithium-ion batteries. Research studies with Si-based anodes have shown stable reversible cycling using electrolytes containing fluoroethylene carbonate (FEC). At the same time, the electrolyte additive, tris(trimethylsilyl) phosphite (TTMSP), has shown to improve the electrochemical performance of nickel-rich layered cathodes, such as LiNi 0.5 Mn 0.3 Co 0.2 O 2 (NMC). However, the combination of these electrolyte additives for the realization of a full-cell NMC-Si lithium-ion battery has not been previously explored. Changes in the electrochemical performance (capacity retention, internal cell resistance, and electrochemical impedance) in half-cells are studied as the ratio of TTMSP and FEC is tuned. At the optimal TTMSP/FEC ratio of 0.33 (T1F3), the NMC-Si full-cells achieve a 2× longer cycle life when compared to the FEC-rich (T0F4) electrolyte. Moreover, T1F3 full-cells demonstrate 1.5 mAh/cm 2 areal capacities and high-capacity retention (25% more than T0F4). A detailed investigation of the electrode-electrolyte interfaces is conducted by using time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). The chemical species depth profiles and elemental analysis illustrate adequate hydrogen fluoride (HF) scavenging. These results demonstrate the synergistic effects of electrolyte additives in minimizing the capacity degradation in NMC-Si full-cells by effectively stabilizing the electrode-electrolyte interfaces.

Risk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22-92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Aim: Identify associations between attitudes of nurses towards people with dementia and their socio-demographic (age and gender) and work-related characteristics (employment, work experience, nursing degree, care setting)., Design: The study was designed in a cross-sectional way, collecting self-reported questionnaire data., Methods: Nurses ( N  = 417) completed the 20-item Dementia Attitude Scale questionnaire, including socio-demographic and work characteristics. Data were analysed using descriptive statistics, group mean comparison, correlation and regression analysis., Results: The attitudes of nurses towards people with dementia were only related to the care setting. Attitudes of nurses working in dementia-specialized long-term care institutions were significantly more positive compared with those working in mixed long-term care institutions and in the homecare setting. The other variables, such as age, gender, employment, nursing degree and work experience, were not associated with the attitudes.

The Traveling Salesman Problem (TSP) is a behavioral test used to measure the efficiency of spatial navigation. It is an optimization problem, in which a number of baited targets are placed in an arena, and as the subject travels between the targets, the route is recorded and compared to chance and optimal routes. The TSP is appealing for the study of learning, memory, and executive function in nonhuman animals because the memory requirements can easily be modified with minor adjustments to task parameters. In the standard version of the task, rats are initially pre-trained to forage for bait in the arena. Once the animals consistently retrieve the bait, they are tested with a set of novel target configurations, and their behavior is recorded. The videos are then scored to produce several measures of performance., (Copyright © 2018 The Authors; exclusive licensee Bio-protocol LLC.)

Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dose-dependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability. Trk receptor expression determined GNF-5837 sensitivity. GNF-5837 caused downregulation of PI3K-Akt-mTOR signaling, Ras-Raf-MEK-ERK signaling, the cell cycle and increased apoptotic cell death. The combinational treatment of GNF-5837 with everolimus showed a significant enhancement in inhibition of cell viability vs single substance treatments, due to a cooperative PI3K-Akt-mTOR and Ras-Raf-MEK-ERK pathway downregulation, as well as an enhanced cell cycle component downregulation. Immunohistochemical staining for Trk receptors were performed using a tissue microarray containing 107 tumor samples of gastroenteropancreatic NETs. Immunohistochemical staining with TrkA receptor and pan-Trk receptor antibodies revealed a positive staining in pancreatic NETs in 24.2% (8/33) and 33.3% (11/33), respectively. We demonstrated that the pan-Trk inhibitor GNF-5837 has promising anti-tumoral properties in human NET cell lines expressing the TrkA receptor. Immunohistochemical or molecular screening for Trk expression particularly in pancreatic NETs might serve as predictive marker for molecular targeted therapy with Trk inhibitors., (© 2018 Society for Endocrinology.)

Context: Anaplastic thyroid carcinoma (ATC) is an orphan disease and confers a dismal prognosis. Standard treatment is not established., Objective: The aim of this study is to describe clinical characteristics, current treatment regimens and outcome of ATC and to identify clinical prognostic markers and treatment factors associated with improved prognosis., Design: Retrospective cohort study at five German tertiary care centers., Patients and Methods: Totally 100 ATC patients diagnosed between 2000 and 2015 were included in the analysis. Disease-specific overall survival (OS) was compared with the Kaplan-Meier method and log-rank test; Cox proportional hazard model was used to identify risk factors., Results: The 6-month, 1-year and 5-year disease-specific OS rates were 37, 28 and 5%, respectively. Stage-dependent OS at 6 months was 78, 54 and 18% for stage IVA, B and C, respectively. 29% patients survived >1 year. Multivariate analysis of OS identified age ≥70 years, incomplete local resection status and the presence of distant metastasis as significant risk factors associated with shorter survival. Radical surgery (hazard ratio [HR] 2.20, 95% confidence interval (CI) 1.19-4.09, P = 0.012), external beam radiation therapy (EBRT) ≥40 Gy (HR = 0.34, 0.15-0.76, P = 0.008) and any kind of chemotherapy (CTX) (HR = 11.64, 2.42-60.39, P = 0.003) were associated with longer survival in multivariate analyses adjusted for age and tumor stage. A multimodal treatment regimen was significantly associated with a survival benefit (HR = 1.04, 1.01-1.08, P < 0.0001) only in IVC patients., Conclusion: Disease-specific OS is still poor in ATC. Treatment factors associated with improved OS provide a rationale to devise treatment pathways for routine care. Collaborative research structures should be aimed to advance treatment of ATC., (© 2016 European Society of Endocrinology.)

The traveling salesman problem (TSP) is used to measure the efficiency of spatial route selection. Among researchers in cognitive psychology and neuroscience, it has been utilized to examine the mechanisms of decision making, planning, and spatial navigation. While both human and non-human animals produce good solutions to the TSP, the solution strategies engaged by non-human species are not well understood. We conducted two experiments on the TSP using Long-Evans laboratory rats as subjects. The first experiment examined the role of arena walls in route selection. Rats tend to display thigmotaxis in testing conditions comparable to the TSP, which could produce results similar to a convex hull type strategy suggested for humans. The second experiment examined the role of turn angle between targets along the optimal route, to determine whether rats exhibit a preferential turning bias. Our results indicated that both thigmotaxis and preferential turn angles do affect performance in the TSP, but neither is sufficient as a predictor of route choice in this task.

Spontaneous recognition of a novel object is a popular measure of exploratory behavior, perception and recognition memory in rodent models. Because of its relative simplicity and speed of testing, the variety of stimuli that can be used, and its ecological validity across species, it is also an attractive task for comparative research. To date, variants of this test have been used with vertebrate and invertebrate species, but the methods have seldom been sufficiently standardized to allow cross-species comparison. Here, we review the methods necessary for the study of novel object recognition in mammalian and non-mammalian models, as well as the results of these experiments. Critical to the use of this test is an understanding of the organism's initial response to a novel object, the modulation of exploration by context, and species differences in object perception and exploratory behaviors. We argue that with appropriate consideration of species differences in perception, object affordances, and natural exploratory behaviors, the spontaneous object recognition test can be a valid and versatile tool for translational research with non-mammalian models.

Purpose: Localized prostate cancer affects younger and healthy patients as well as older patients with comorbidities. The purpose of this study was to evaluate the effect of age and comorbidities on the quality-of-life (QoL) course before and after radical retropubic prostatectomy., Patients and Methods: Overall, 374 patients with localized prostate cancer scheduled for radical prostatectomy were prospectively included. The QoL questionnaire QLQ-C30 (European Organisation for Research and Treatment of Cancer) was completed 1 day before surgery and 3, 6, 9, and 12 months after radical prostatectomy. Sexual and urinary functions were not assessed in this analysis. Subgroups according to age at diagnosis (≤60,>60 to≤70, and>70y) and comorbidities (Charlson scores≤2 and ≥3) were defined. Subgroups were compared using the Wilcoxon-Mann-Whitney test, whereas changes in a group over time were analyzed with the Wilcoxon signed rank test., Results: In all patient groups, no change was found 12 months after surgery compared with preoperative values in global health as well as functioning (role, physical, cognitive, and social). Emotional functioning improved significantly after surgery compared with preoperative functioning. Older patients (>70y) had better emotional and social functioning compared with younger patients (≤60y). The other scores were comparable between older and younger patients. Global health and physical, role, cognitive, and social functioning were independent of the number of comorbidities, although patients with a Charlson score≥3 did worse regarding fatigue and dyspnoe., Conclusion: The QoL of older patients or patients with multiple comorbidities is not negatively influenced by radical prostatectomy. This should be considered when discussing the indication for prostatectomy in older or comorbid patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Context: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy., Objective: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS., Design: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years., Patients: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease., Results: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses., Conclusions: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Objective: Bilateral adrenalectomy (BADX) is an important treatment option for patients with Cushing's syndrome (CS). Our aim is to analyze the long-term outcomes, surgical, biochemical, and clinical as well as morbidity and mortality, of patients who underwent BADX., Design: A total of 50 patients who underwent BADX since 1990 in two German centers were identified. Of them, 34 patients had Cushing's disease (CD), nine ectopic CS (ECS), and seven ACTH-independent bilateral adrenal hyperplasia (BAH)., Methods: Standardized follow-up examination was performed in 36 patients with a minimum follow-up time of 6 months after BADX and a median follow-up time of 11 years., Results: Surgical morbidity and mortality were 6 and 4% respectively. All patients were found to be in remission after BADX. Almost all Cushing's-specific comorbidities except for psychiatric diseases improved significantly. Health-related quality of life remained impaired in 45.0% of female and 16.7% of male patients compared with a healthy population. The median number of adrenal crises per 100 patient-years was four. Nelson tumor occurred in 24% of CD patients after a median time span of 51 months. Long-term mortality after 10 years was high in ECS (44%) compared with CD (3%) and BAH (14%)., Conclusions: BADX is an effective and relatively safe treatment option especially in patients with CD. The majority of patients experience considerable improvement of Cushing's symptoms., (© 2014 European Society of Endocrinology.)

The past decade has seen rapid proliferation of behavioral research with zebrafish, and an emergence of interest in their potential as a model of neurocognitive function. Already, zebrafish have been proposed as a model of autism, Alzheimer's, drug abuse, schizophrenia, and other disorders involving cognitive dysfunction. Zebrafish have the sophisticated sensory and motor systems necessary for complex learning experiments, and their power as a genetic and developmental model has already been established. Currently, however, learning procedures remain unrefined, and behavioral variability presents a major problem for researchers. Before zebrafish can be effectively used to study the neurological bases of learning, a set of robust and replicable techniques must be characterized and standardized. The purpose of this review is to provide an overview and critique of learning procedures that have been used with zebrafish and their results. We hope that such an analysis will prove useful in this early stage of research to guide future learning experiments and thereby improve the efficiency and validity of research with this promising new animal model., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Performance on a typical pen-and-paper (figural) version of the Traveling Salesman Problem was compared to performance on a room-sized navigational version of the same task. Nine configurations were designed to examine the use of the nearest-neighbor (NN), cluster approach, and convex-hull strategies. Performance decreased with an increasing number of nodes internal to the hull, and improved when the NN strategy produced the optimal path. There was no overall difference in performance between figural and navigational task modalities. However, there was an interaction between modality and configuration, with evidence that participants relied more heavily on the NN strategy in the figural condition. Our results suggest that participants employed similar, but not identical, strategies when solving figural and navigational versions of the problem. Surprisingly, there was no evidence that participants favored global strategies in the figural version and local strategies in the navigational version.

Although the number of incidents is unknown, professional quality-oriented renal organizations have become aware of an increased number of complaints regarding nephrologists who approach patients with the purpose of influencing patients to change nephrologists or dialysis facilities (hereinafter referred to as patient solicitation). This development prompted the Forum of ESRD Networks and the Renal Physicians Association to publish a policy statement on professionalism and ethics in medical practice as these concepts relate to patient solicitation. Also common but not new is the practice of nephrologists trying to recruit their own patients to a new dialysis unit in which they have a financial interest. This paper presents two illustrative cases and provides an ethical framework for analyzing patient solicitation and physician conflict of interest. This work concludes that, in the absence of objective data that medical treatment is better elsewhere, nephrologists who attempt to influence patients to change nephrologists or dialysis facilities fall short of accepted ethical standards pertaining to professional conduct, particularly with regard to the physician-patient relationship, informed consent, continuity of care, and conflict of interest.

In light of the massive uncertainty with both the federal government in general and health policy priorities specifically, it is probably constructive to focus on the things we know for sure. In Medicare Part B reimbursement, the SGR system is fundamentally flawed, and must be replaced. All of Congress has recognized this fact, and there is legislation in the House that would move the ball forward on SGR repeal and replacement. Likewise, coordinated care models like ACOs offer a logical process for achieving a triple aim: improving individual health care, improving population health, and promoting cost efficiency in health care. Hopefully, policy makers in Washington will recognize and act on these truths as well.

Neuromuscular adaptations during skill acquisition have been extensively investigated for skeletal muscles. Motor rehabilitation is the main target for application of motor training. Such measures are also relevant for the musculature of the jaw, but few data are available for motor adaptation of the masticatory system. The objective of this study was to evaluate and compare long-term training effects of different motor tasks on masseter and temporal muscles. In 20 healthy subjects, the electromyographic response to unilateral and bilateral maximum voluntary tooth clenching, balancing the mandible on a hydrostatic system under force-feedback-controlled conditions, and unilateral chewing was investigated in an initial session and then in two follow-up sessions separated by 2 and 10 weeks from baseline. Motor tasks were repeated three times for chewing, nine times for maximum biting (MB) and 24 times for the coordination tasks (CT). The sequences of the various motor tasks were applied once in the first session and twice in the second and third sessions. No effects of training were observed for MB tasks except for MB in intercuspation, for which significant yet transient avoidance behaviour occurred in the second session. No significant effects were found for chewing tests. For the CT, however, a robust significant long-term training effect was detected which reduced the electric muscle activity in session 2 by approximately 20% and in session 3 by approximately 40% compared with the initial measurements. The study showed that the masticatory muscles are remarkably prone to motor adaptation if demanding CT must be accomplished., (© 2011 Blackwell Publishing Ltd.)

Ethanol has been suggested to have an anxiolytic effect on zebrafish, primarily based on its disruption of the novel tank diving response and of some social behaviors. The light/dark preference test offers a complementary measure of anxiety-like behavior in fish, and the purpose of the current study was to determine the effects of acute ethanol exposure on behavior in the light/dark task. In Experiment 1, the stimuli used to induce light/dark preference in zebrafish were varied in order to determine how best to measure the behavior. Subjects exhibited phototaxis (preference for light) when illumination was manipulated, but scototaxis (preference for dark) when wall and substrate color were manipulated. There was a clear interaction between locomotor activity and color preference, with animals preferentially freezing in darker locations. Because of ambiguity in interpreting behavior in the open/covered version of the test, the black/white version was used in Experiment 2. In Experiment 2, zebrafish were exposed to ethanol (0.25%, 0.5%, or 1.0%) or water for 30 minutes, and then placed in a black/white preference tank containing either ethanol (same doses) or water for a 30-minute test. Ethanol exposure increased locomotor activity and reduced freezing. Additionally, there was a significant interaction between ethanol treatment and locomotor activity on side preference. Low doses of ethanol increased white avoidance in normally swimming fish, while high doses did not., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Alterations of body sway caused by isometric contractions of the jaw muscles have been reported previously. The objective of this study was to test if motor tasks of the masticatory system with different control demands affect body posture differently during quiet stance. Position and sway displacements of the center of foot pressure (COP) were measured for 20 healthy subjects who either kept the mandible at rest or performed unilateral and bilateral maximum voluntary teeth clenching, feedback-controlled biting tasks at submaximum bite forces, or unilateral chewing. Two weeks later the measurements were repeated. Compared with quiet stance, the COP results revealed significant changes during the feedback-controlled biting tasks. Robust sway reduction and anterior displacement of the COP were observed under these conditions. Body oscillations were not significantly affected by maximum bites or by unilateral chewing. For most of the variables investigated there were no significant differences between unilateral and bilateral biting. Robust sway reduction during feedback-controlled biting tasks in healthy subjects involved a stiffening phenomenon that was attributed to the common physiological repertoire of posture control, and might optimize the stability of posture under these conditions., (© 2011 Blackwell Publishing Ltd.)

We present a new approach for constructing optical phase-space-time-frequency tomography (OPSTFT) of an optical wave field. This tomography can be measured by using a novel four-window optical imaging system based on two local oscillator fields balanced heterodyne detection. The OPSTFT is a Wigner distribution function of two independent Fourier Transform pairs, i.e., phase-space and time-frequency. From its theoretical and experimental aspects, it can provide information of position, momentum, time and frequency of a spatial light field with precision beyond the uncertainty principle. Besides the distributions of x-p and t-ω, the OPSTFT can provide four other distributions such as x-t, p-t, x-ω and p-ω. We simulate the OPSTFT for a light field obscured by a wire and a single-line absorption filter. We believe that the four-window system can provide spatial and temporal properties of a wave field for quantum image processing and biophotonics., (© 2011 Optical Society of America)

Objective: The present study evaluates the long-term effects of a preschool training in phonological awareness and letter- sound correspondence., Method: The children from the experimental and the control group of the original study (Blaser et al., 2007) were retested by means of reading and writing tests at the end of the 3rd and 4th grades., Results: Results reveal no significant difference between the trained group and the control group with regard to their average reading and writing performance. Effects of the training are seen in the reduction of the number of children with spelling problems in the trained group. The training had no detectable positive effects on the percentage of children with reading problems., Conclusions: In summary, results are interpreted as a confirmation of the effectiveness of the training in the primary prevention of spelling problems. In spite of these results a small percentage of children remains that develops reading and spelling problems despite having participated in the preventive intervention. Future research should focus upon these children.

While zebrafish may be a useful behavioral model of human anxiety, it is not obvious which behaviors are accurate measures of anxiety in zebrafish. Beginning with the premise that the most fundamental indicator of fear is avoidance, the goal of the current study was to determine which behaviors are systematically observed in the presence of an avoided stimulus. In a dark/bright preference task, adult zebrafish preferred a black chamber and avoided a white chamber. Then, subjects were confined to each chamber, and their behaviors recorded. A principal component analysis was used to determine which behaviors clustered with the tendency to avoid white. Additionally, the behaviors of High-avoidant and Low-avoidant animals were compared using analysis of variance. Results indicate that confinement to white systematically elicited freezing in animals with a strong dark preference, but not in animals with little preference. Turn rate (erratic movement) was weakly related to avoidance, while thigmotaxis and locomotor activity were poor predictors. Freezing is therefore suggested to be a viable measure of white-induced anxiety, while interpretation of the other behaviors is more ambiguous and will require further investigation., (Copyright 2009 Elsevier B.V. All rights reserved.)

In short, the lessons of this story are: Don't eat at a place called "Ma's". Don't play poker with a man named Doc. Don't go too far out on a limb making predictions in the 21st century's U.S. health policy arena.

These are times of turbulence and change at many levels-for the nation at large, within the health care delivery arena broadly, and for nephrology specifically. The factors outlined above have created a degree of complexity in developing solutions for these issues never seen before. We'll see how the next 12 months unfolds.

It has long been suspected in the vertebrate literature, but demonstrated only recently in work with honeybees (Apis mellifera), that the different treatments of nontarget stimuli in conventional between-groups blocking experiments may give the appearance of blocking independently of experience with the target stimulus. The same difficulty does not arise in within-subjects experiments, and in a series of such experiments with odors and colors free-flying honeybees gave no evidence of blocking; separate reinforced presentations of one element of a reinforced compound failed to reduce responding to the second. There was, however, clear evidence of facilitation; separate nonreinforced presentations of one element of a reinforced compound increased responding to the second. The implications of the results for further work on compound conditioning in honeybees and other animals are considered., ((PsycINFO Database Record (c) 2008 APA, all rights reserved).)

There is little good news on the physician payment front for all of organized medicine in general, and for specifically nephrology. While the CHAMP bill is a clear indicator of recognition among some legislators that fundamental change is necessary in the near future, the factors complicating efforts to make that change happen are numerous and substantial. Details on the resolution of physician reimbursement issues for 2008 and how these issues may develop for 2009 will be outlined on the RPA website at www.renalmd.org as they become available.

Clinical pathways are an effective instrument to decrease undesired practice variability and improve clinician performance. IT-applications embedded into clinical routine work can help to increase pathway compliance. Successfully implementing such applications requires both a responsive IT infrastructure and a participatory and iterative design process aimed at achieving user acceptance and usability. Experiences from the implementation and iterative improvement of an online surgical pathway at Marburg University Medical Centre have shown that pathway conformance actually could be improved by the use of IT. An analysis of the iterative design process has shown that future pathway projects can benefit from the lessons learned during this project. Based on these lessons recommendations for developing well adapted interaction mechanisms are presented, aimed at improving process alignment. Our goal is to build up a library of tested reusable components to reduce the number of iterations for pathway implementation.

Objective: The present study intended to evaluate the short-, middle and long-term effects of preschool training in phonological awareness and letter-sound correspondence, conducted in Swiss dialect in Swiss kindergartens, on the basis of the outcome variables phonological awareness and reading and spelling competence., Method: From a total sample of 109 children with complete datasets over all measurement points, a paired sample of 26 children each from the experimental and from the control group was selected for statistical analyses. Evaluated on the one hand were the short- middle and longer-term effects of the training on the development of the phonological awareness, while on the other, the average reading and spelling competencies and the percentage of reading-and-spelling disabled children in the training and in the control group were compared for the 1st and 2nd grades., Results: Effects of the training on phonological awareness could be documented up to the beginning of the 1st grade. The average reading and spelling competencies did not differ be-tween the groups, whereas the percentage of spelling-disabled children was markedly reduced in the training group., Conclusions: As a whole, the results are seen as a confirmation of the efficacy of the training in the primary prevention of reading and writing disorders.

To deliver patient-specific advice at the time and place of a consultation is an important contribution to improving clinician performance. Using computer-based decision support on the basis of clinical pathways is a promising strategy to achieve this goal. Thereby integration of IT applications into the clinical workflow is a core precondition for success. User acceptance and usability play a critical role: additional effort has to be balanced with enough benefit for the users and interaction design and evaluation should be handled as an intertwined, continuous process. Experiences from routine use of an online surgical pathway at Marburg University Medical Center show that it is possible to successfully address this issue by seamlessly integrating patient-specific pathway recommendations with documentation tasks which have to be done anyway, by substantially reusing entered data to accelerate routine tasks (e.g. by automatically generating orders and reports), and by continuously and systematically monitoring pathway conformance and documentation quality.

The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the zebrafish may be utilized in this line of research. Previously, we investigated the effects of acute ethanol exposure on adult zebrafish using four behavioral paradigms and employing manual quantification methods. Here, we study the effects of chronic ethanol exposure and analyze how it modifies the effects of acute ethanol treatment. We employ a videotracking-based automated quantification method in a predator model paradigm and show that this method is capable of detecting an avoidance reaction that is ameliorated by higher doses of ethanol, a potential anxiolytic effect. Importantly, we also demonstrate that chronic, two week long, exposure to ethanol results in significant adaptation to this substance in adult zebrafish. Overall, our results suggest that zebrafish will be an appropriate subject for high throughput screening applications aimed at the analysis of the mechanisms and pharmacology of acute and chronic ethanol induced changes in the vertebrate brain.

The zebrafish has been popular in developmental biology and genetics, but its brain function has rarely been studied. High-throughput screening of mutation or drug-induced changes in brain function requires simple and automatable behavioral tests. This article compares three behavioral quantification methods in four simple behavioral paradigms that test a range of characteristics of adult zebrafish, including novelty-induced responses, social behavior, aggression, and predator-model-induced responses. Two quantification methods, manual recording and computerized videotracking of location and activity, yielded very similar results, suggesting that automated videotracking reliably measures activity parameters and will allow high-throughput screening. However, observation-based event recording of posture patterns was found generally not to correlate with videotracking measures, suggesting that further refinement of automated behavior quantification may be considered.

Clinical pathways are an effective instrument to decrease undesired practice variability and improve clinician performance. IT applications embedded into clinical routine work can help to increase pathway compliance. Successfully implementing such applications requires both a responsive IT infrastructure and a participatory and iterative design process aimed at achieving user acceptance and usability. Experiences from the implementation and iterative improvement of an online surgical pathway at Marburg University Medical Centre have shown that pathway conformance actually could be improved by the use of IT. An analysis of the iterative design process has shown that future pathway projects can benefit from the lessons learned during this project. Based on these lessons a method for developing well adapted interaction mechanisms is presented, which is aimed at improving process alignment. Our goal is to build up a library of tested reusable components to reduce the number of iterations for pathway implementation.

Prompted by doubts about the adequacy of the various control procedures long used in research on blocking, we repeated some earlier experiments with honeybees that had given the appearance of forward, concurrent, and backward blocking. The new experiments differed from the earlier experiments only in that the target stimulus was omitted during the training and was encountered for the first time in the test. In the new experiments, just as in the earlier experiments, the blocking groups responded less to the target stimulus than did the control groups. The results show that the effects of the different treatments of nontarget stimuli commonly compared in blocking experiments may generalize to the target stimulus and thus affect responding to that stimulus independently of experience with it. Implications for research on blocking in honeybees and other animals are considered.

The aim of this study was to investigate (i) whether the masseter muscle shows differential activation under experimental conditions which simulate force generation during clenching and grinding activities; and (ii) whether there are (a) preferentially active muscle regions or (b) force directions which show enhanced muscle activation. To answer these questions, the electromyographic (EMG) activity of the right masseter muscle was recorded with five intramuscular electrodes placed in two deep muscle areas and in three surface regions. Intraoral force transfer and force measurement were achieved by a central bearing pin device equipped with three strain gauges (SG). The activity distribution in the muscle was recorded in four different mandibular positions (central, left, right, anterior). In each position, maximum voluntary contraction (MVC) was exerted in vertical, posterior, anterior, medial and lateral directions. The investigated muscle regions showed different amount of EMG activity. The relative intensity of the activation, with respect to other regions, changed depending on the task. In other words, the muscle regions demonstrated heterogeneous changes of the EMG pattern for the various motor tasks. The resultant force vectors demonstrated similar amounts in all horizontal bite directions. Protrusive force directions revealed the highest relative activation of the masseter muscle. The posterior deep muscle region seemed to be the most active compartment during the different motor tasks. The results indicate a heterogeneous activation of the masseter muscle under test conditions simulating force generation during clenching and grinding. Protrusively directed bite forces were accompanied by the highest activation in the muscle, with the posterior deep region as the most active area.

To deliver patient-specific advice at the time and place of a consultation, to improve clinician performance and compliance by using computer-based decision support, and to integrate such IT solutions with the clinical workflow are important strategies for the implementation of clinical pathways. User acceptance plays a critical role: additional effort has to be balanced with enough benefit for the users. Experiences from routine use of an online surgical pathway at Marburg University Medical Center show that it is possible to successfully address this issue by seamlessly integrating patient-specific pat documentation tasks which have to be done anyway and by substantially reusing entered data to accelerate routine tasks (e.g. by automatically generating orders and reports).

Three experiments with foraging honeybees were designed to study the effect of experience with A on responding to B after AB+ training. In the first experiment, responding to B was the same whether the AB+ training was preceded or followed by A+ training. In the second experiment, responding to B after AB+ training was less in animals that also had A+ training than in control animals that were equally often reinforced in the absence of A; whether the A+ training preceded, was concurrent with, or followed the AB+ training made no difference. In the third experiment, responding to B after AB+ training was less when the AB+ training was followed by A+C- training than when it was followed by C+/A- training. These results, like those of some recent vertebrate experiments, take us beyond the traditional explanation of blocking in terms of impaired conditioning of B on AB+ trials and support the suggestion that the mechanism, still poorly understood, may nevertheless be a relatively simple one.

Marburg University Medical Center has been introducing a comprehensive health information system since 1999, using a single-vendor application framework with an integrated generator tool for the development of clinical applications. To find out if this architecture and our participative software engineering approach can be considered a step towards a responsive infrastructure, we compared the situation after the first deployment phase (basically a holistic approach) with the situation after the system was further developed and adapted to the users' needs using the generator tool approach. We collected system statistics and conducted user satisfaction surveys in 2001/02 and 2003 using standardized measurements. The survey results showed that user involvement as well as system content were judged significantly higher after the second deployment phase. Insofar, we could demonstrate the feasibility of our approach. However, definite statements concerning the superiority of the generator tool approach to other concepts are not yet possible. We will continue our assessment, and we strongly suggest further studies in other institutions introducing comparable clinical functionality.

The past decade has seen ongoing debate regarding federal support of graduate medical education, with numerous proposals for reform. Several critical problems with the current mechanism are evident on reviewing graduate medical education (GME) funding issues from the perspectives of key stakeholders. These problems include the following: substantial interinstitutional and interspecialty variations in per-resident payment amounts; teaching costs that have not been recalibrated since 1983; no consistent control by physician educators over direct medical education (DME) funds; and institutional DME payments unrelated to actual expenditures for resident education or to program outcomes. None of the current GME reform proposals adequately address all of these issues. Accordingly, we recommend several fundamental changes in Medicare GME support. We propose a re-analysis of the true direct costs of resident training (with appropriate adjustment for local market factors) to rectify the myriad problems with per-resident payments. We propose that Medicare DME funds go to the physician organization providing resident instruction, keeping DME payments separate from the operating revenues of teaching hospitals. To ensure financial accountability, we propose that institutions must maintain budgets and report expenditures for each GME program. To establish educational accountability, Residency Review Committees should establish objective, annually measurable standards for GME program performance; programs that consistently fail to meet these minimum standards should lose discretion over GME funds. These reforms will solve several long-standing, vexing problems in Medicare GME funding, but will also uncover the extent of undersupport of GME by most other health care payers. Ultimately, successful reform of GME financing will require "all-payer" support.

Due to typical problems (heterogeneity, lack of clinical functionality, Y2K problems) the board of directors of the university hospital of Marburg decided in 1997 to replace major components of the existing system by commercially available software. The products available on the market were analyzed, and, under participation of different user groups, a comprehensive functional specification was generated. This was the basis for a Europe-wide vendor selection process. In this context, several key aspects were identified, which are critically important for realizing a HIS that fulfills the specified functional requirements. Among these key aspects are the integration of heterogeneous system components, the support of cross-departmental workflow, and flexibility as well as adaptability to specific clinical requirements. As a result, we found that with today's commercially available products and standards there is no single solution that fully meets all requirements. However, some "generalist" vendors are offering integrated systems with acceptable clinical functionality. Tools are emerging which enable the clinical user to generate forms for data input and data flow. Still, a hospital information system will consist of separate components that have to be integrated, but the role of integrated, component-based approaches is becoming more important.