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1.  Direct lexical control of eye movements in reading: Evidence from a survival analysis of fixation durations 
Cognitive psychology  2012;65(2):177-206.
Participants’ eye movements were monitored in an experiment that manipulated the frequency of target words (high vs. low) as well as their availability for parafoveal processing during fixations on the pre-target word (valid vs. invalid preview). The influence of the word-frequency by preview validity manipulation on the distributions of first fixation duration was examined by using ex-Gaussian fitting as well as a novel survival analysis technique which provided precise estimates of the timing of the first discernible influence of word frequency on first fixation duration. Using this technique, we found a significant influence of word frequency on fixation duration in normal reading (valid preview) as early as 145 ms from the start of fixation. We also demonstrated an equally rapid non-lexical influence on first fixation duration as a function of initial landing position (location) on target words. The time-course of frequency effects, but not location effects was strongly influenced by preview validity, demonstrating the crucial role of parafoveal processing in enabling direct lexical control of reading fixation times. Implications for models of eye-movement control are discussed.
doi:10.1016/j.cogpsych.2012.03.001
PMCID: PMC3565237  PMID: 22542804
Eye movements; Reading; Lexical processing; Word frequency; Parafoveal preview; Direct control; Initial landing position; Fixation location; Fixation duration
2.  The Emergence of Frequency Effects in Eye Movements 
Cognition  2012;123(1):185-189.
A visual search experiment employed strings of Landolt Cs to examine how the gap size of and frequency of exposure to distractor strings affected eye movements. Increases in gap size were associated with shorter first-fixation durations, gaze durations, and total times, as well as fewer fixations. Importantly, both the number and duration of fixations decreased with repeated exposures. The findings provide evidence for the role of cognition in guiding eye-movements, and a potential explanation for word-frequency effects observed in reading.
doi:10.1016/j.cognition.2011.12.011
PMCID: PMC3278573  PMID: 22264379
eye-movement control; word frequency effects; reading; visual search
3.  Eye movements in reading versus nonreading tasks: Using E-Z Reader to understand the role of word/stimulus familiarity 
Visual cognition  2012;20(4-5):360-390.
In this article, we extend our previous work (Reichle, Pollatsek, & Rayner, 2012) using the principles of the E-Z Reader model to examine the factors that determine when and where the eyes move in both reading and non-reading tasks, and in particular the role that word/stimulus familiarity plays in determining when the eyes move from one word/stimulus to the next. In doing this, we first provide a brief overview of E-Z Reader, including its assumption that word familiarity is the “engine” driving eye movements during reading. We then review the theoretical considerations that motivated this assumption, as well as recent empirical evidence supporting its validity. We also report the results of three new simulations that were intended to demonstrate the utility of the familiarity check in three tasks: (1) reading; (2) searching for a target word in embedded in text; and (3) searching for the letter O in linear arrays of Landolt Cs. The results of these simulations suggest that the familiarity check always improves task efficiency by speeding its rate of performance. We provide several arguments as to why this conclusion is not likely to be true for the two non-reading tasks, and in the final section of the paper, we provide a fourth simulation to test the hypothesis that problems associated with the mis-identification of words may also curtail the too liberal use of word familiarity.
doi:10.1080/13506285.2012.667006
PMCID: PMC3374660  PMID: 22707910
4.  Neurophysiological constraints on the eye-mind link 
Several current computational models of eye-movement control in reading posit a tight link between the eye and mind, with lexical processing directly triggering most “decisions” about when to start programming a saccade to move the eyes from one word to the next. One potential problem with this theoretical assumption, however, is that it may violate neurophysiological constraints imposed by the time required to encode visual information, complete some amount of lexical processing, and then program a saccade. In this article, we review what has been learned about these timing constraints from studies using ERP and MEG. On the basis of this review, it would appear that the temporal constraints are too severe to permit direct lexical control of eye movements without a significant amount of parafoveal processing (i.e., pre-processing of word n+1 from word n). This conclusion underscores the degree to which the perceptual, cognitive, and motor processes involved in reading must be highly coordinated to support skilled reading, a par excellence example of a task requiring visual-cognitive expertise.
doi:10.3389/fnhum.2013.00361
PMCID: PMC3710954  PMID: 23874281
ERP; MEG; computational models; reading; saccades
5.  Parafoveal preview during reading: Effects of sentence position 
Two experiments examined parafoveal preview for words located in the middle of sentences and at sentence boundaries. Parafoveal processing was shown to occur for words at sentence-initial, mid-sentence, and sentence-final positions. Both Experiments 1 and 2 showed reduced effects of preview on regressions out for sentence-initial words. In addition, Experiment 2 showed reduced preview effects on first-pass reading times for sentence-initial words. These effects of sentence position on preview could result from reduced parafoveal processing for sentence-initial words, or other processes specific to word reading at sentence boundaries. In addition to the effects of preview, the experiments also demonstrate variability in the effects of sentence wrap-up on different reading measures, indicating that the presence and time course of wrap-up effects may be modulated by text-specific factors. We also report simulations of Experiment 2 using version 10 of E-Z Reader (Reichle, Warren, & McConnell, 2009), designed to explore the possible mechanisms underlying parafoveal preview at sentence boundaries.
doi:10.1037/a0022190
PMCID: PMC3140553  PMID: 21500948
reading; eye movements; E-Z Reader; parafoveal preview; wrap-up effects
6.  The Influence of Climatic Seasonality on the Diversity of Different Tropical Pollinator Groups 
PLoS ONE  2011;6(11):e27115.
Tropical South America is rich in different groups of pollinators, but the biotic and abiotic factors determining the geographical distribution of their species richness are poorly understood. We analyzed the species richness of three groups of pollinators (bees and wasps, butterflies, hummingbirds) in six tropical forests in the Bolivian lowlands along a gradient of climatic seasonality and precipitation ranging from 410 mm to 6250 mm. At each site, we sampled the three pollinator groups and their food plants twice for 16 days in both the dry and rainy seasons. The richness of the pollinator groups was related to climatic factors by linear regressions. Differences in species numbers between pollinator groups were analyzed by Wilcoxon tests for matched pairs and the proportion in species numbers between pollinator groups by correlation analyses. Species richness of hummingbirds was most closely correlated to the continuous availability of food, that of bees and wasps to the number of food plant species and flowers, and that of butterflies to air temperature. Only the species number of butterflies differed significantly between seasons. We were not able to find shifts in the proportion of species numbers of the different groups of pollinators along the study gradient. Thus, we conclude that the diversity of pollinator guilds is determined by group-specific factors and that the constant proportions in species numbers of the different pollinator groups constitute a general pattern.
doi:10.1371/journal.pone.0027115
PMCID: PMC3206942  PMID: 22073268
7.  Models of the Reading Process 
Reading is a complex skill involving the orchestration of a number of components. Researchers often talk about a “model of reading” when talking about only one aspect of the reading process (for example, models of word identification are often referred to as “models of reading”). Here, we review prominent models that are designed to account for (1) word identification, (2) syntactic parsing, (3) discourse representations, and (4) how certain aspects of language processing (e.g., word identification), in conjunction with other constraints (e g., limited visual acuity, saccadic error, etc.), guide readers’ eyes. Unfortunately, it is the case that these various models addressing specific aspects of the reading process seldom make contact with models dealing with other aspects of reading. Thus, for example, the models of word identification seldom make contact with models of eye movement control, and vice versa. While this may be unfortunate in some ways, it is quite understandable in other ways because reading itself is a very complex process. We discuss prototypical models of aspects of the reading process in the order mentioned above. We do not review all possible models, but rather focus on those we view as being representative and most highly recognized.
doi:10.1002/wcs.68
PMCID: PMC3001687  PMID: 21170142
8.  Lexical and Post-Lexical Complexity Effects on Eye Movements in Reading 
The current study investigated how a post-lexical complexity manipulation followed by a lexical complexity manipulation affects eye movements during reading. Both manipulations caused disruption in all measures on the manipulated words, but the patterns of spill-over differed. Critically, the effects of the two kinds of manipulations did not interact, and there was no evidence that post-lexical processing difficulty delayed lexical processing on the next word (c.f. Henderson & Ferreira, 1990). This suggests that post-lexical processing of one word and lexical processing of the next can proceed independently and likely in parallel. This finding is consistent with the assumptions of the E-Z Reader model of eye movement control in reading (Reichle, Warren, & McConnell, 2009).
PMCID: PMC3097123  PMID: 21603125
Reading; sentence complexity; eye movements; E-Z Reader; word frequency
9.  Renal function during rofecoxib therapy in patients with metastatic cancer: retrospective analysis of a prospective phase II trial 
BMC Research Notes  2011;4:2.
Background
Angiostatic/antiinflammatory therapy with COX-II inhibitors and pioglitazone seems to be a well tolerated and promising regimen in patients with metastatic cancer. COX-II inhibitors may have less gastrointestinal side effects than conventional non-steroidal antiinflammatory drugs, but their impact on renal function seems to be similar.
Methods
87 patients with metastatic/advanced cancer were treated up to 12 months (mean 19.5 weeks) with rofecoxib, pioglitazone and either capecitabine (group A with gastrointestinal and urological cancer, n = 50) or trofosfamide (group B with non-gastrointestinal/non-urological cancer, n = 37) and followed for further 6 months.
Results
Baseline serum creatinine concentration was 0.81 ± 0.28 mg/dl, and increased by about 0.15 mg/dl during months 1-3. Accordingly estimated glomerular filtration rate (eGFR) decreased from 90.3 ml/min ± 3.6 ml/min at baseline by about 10 ml/min during months 1-3. Renal function decreased in 75 patients (86%) in the first month (p < 0.0001). This decrease went along with clinical signs of volume expansion. Renal function tended to recover after discontinuation of the study medication.
Conclusions
Therapy with rofecoxib in an antiangiogenic/antiinflammatory setting results in a decrease of renal function in nearly every patient.
Trial registration number
German Clinical Trials Register DRKS: DRKS00000119
doi:10.1186/1756-0500-4-2
PMCID: PMC3038926  PMID: 21208422
10.  Eye Movements and Non-Canonical Reading: Comments on Kennedy and Pynte (2008) 
Vision research  2008;49(17):2232-2236.
Kennedy and Pynte (2008) presented data that they suggested pose problems for models of eye movement control in reading in which words are encoded serially. They focus on situations in which pairs of words are fixated out of order (i.e., the first word is skipped and the second fixated prior to a regression back to the first word). We strongly disagree with their claims and contest their arguments. We argue that their data set was obtained selectively and the events they believe are problematic do not occur frequently during reading. Furthermore, we do not consider that Kennedy and Pynte’s arguments pose serious difficulties for serial models of reading such as E-Z Reader.
doi:10.1016/j.visres.2008.10.013
PMCID: PMC2746070  PMID: 19000705
11.  Investigating the causes of wrap-up effects: Evidence from eye movements and E-Z Reader 
Cognition  2009;111(1):132-137.
Wrap-up effects in reading have traditionally been thought to reflect increased processing associated with intra- and inter-clause integration (Just & Carpenter, 1980; Rayner, Kambe & Duffy, 2000; cf. Hirotani, Frazier, & Rayner, 2006). We report an eye-tracking experiment with a strong manipulation of integrative complexity at a critical word that was either sentence-final, ended a comma-marked clause, or was not comma marked. Although both complexity and punctuation each had reliable effects, they did not interact in any eye-movement measure. These results and simulations using the E-Z Reader model of eye-movement control (Reichle, Warren, & McConnell, 2009) suggest that traditional accounts of clause wrap-up are incomplete.
doi:10.1016/j.cognition.2008.12.011
PMCID: PMC2682724  PMID: 19215911
12.  Principles of Modular Tumor Therapy 
Cancer Microenvironment  2009;2(Suppl 1):227-237.
Nature is interwoven with communication and is represented and reproduced through communication acts. The central question is how may multimodal modularly acting and less toxic therapy approaches, defined as modular therapies, induce an objective response or even a continuous complete remission, although single stimulatory or inhibitingly acting drugs neither exert mono-activity in the respective metastatic tumor type nor are they directed to potentially ‘tumor-specific’ targets. Modularity in the present context is a formal pragmatic communicative systems concept, describing the degree to which systems objects (cells, pathways etc.) may be communicatively separated in a virtual continuum, and recombined and rededicated to alter validity and denotation of communication processes in the tumor. Intentional knowledge, discharging in reductionist therapies, disregards the risk-absorbing background knowledge of the tumor’s living world including the holistic communication processes, which we rely on in every therapy. At first, this knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. All communication-relevant steps, such as intentions, understandings, and the appreciation of messages, may be modulated simultaneously, even with a high grade of specificity. Thus, modular therapy approaches including risk-absorbing and validity-modifying background knowledge may overcome reductionist idealizations. Modular therapies show modular events assembled by the tumor’s living world as an additional evolution-constituting dimension. This way, modular knowledge may be acquired from the environment, either incidentally or constitutionally. The new communicatively defined modular coherency of environment, i.e. the tumor-associated microenvironment, and tumor cells open novel ways for the scientific community in ‘translational medicine’.
doi:10.1007/s12307-009-0023-x
PMCID: PMC2756340  PMID: 19593676
Evolution; Inflammation; Metastatic tumor; Personalized therapy; Systems assessment tools; Systems biology
13.  Lost in the Sauce The Effects of Alcohol on Mind Wandering? 
Psychological science  2009;20(6):747-752.
Alcohol consumption alters consciousness in ways that make drinking both alluring and hazardous. Recent advances in the study of consciousness using a mind-wandering paradigm permit a rigorous examination of the effects of alcohol on experiential consciousness and metaconsciousness. Fifty-four male social drinkers consumed alcohol (0.82 g/kg) or a placebo beverage and then performed a mind-wandering reading task. This task indexed both self-caught and probe-caught zone-outs to distinguish between mind wandering inside and outside of awareness. Compared with participants who drank the placebo, those who drank alcohol were significantly more likely to report that they were zoning out when probed. After this increase in mind wandering was accounted for, alcohol also lowered the probability of catching oneself zoning out. The results suggest that alcohol increases mind wandering while simultaneously reducing the likelihood of noticing one's mind wandering. Findings are discussed with regard to theories of alcohol and theories of consciousness.
doi:10.1111/j.1467-9280.2009.02351.x
PMCID: PMC2724753  PMID: 19422627
14.  Serial or Parallel? Using Depth-of-Processing to Examine Attention Allocation During Reading 
Vision research  2008;48(17):1831-1836.
This paper presents an experiment investigating attention allocation in four tasks requiring varied degrees of lexical processing of 1-4 simultaneously displayed words. Response times and eye movements were only modestly affected by the number of words in the asterisk-detection task but increased markedly with the number of words in the letter-detection, rhyme-judgment, and semantic-judgment tasks, suggesting that attention may not be serial for tasks that do not require significant lexical processing (e.g., detecting visual features), but is approximately serial for tasks that do (e.g., retrieving word meanings). The implications of these results for models of readers’ eye movements are discussed.
doi:10.1016/j.visres.2008.05.007
PMCID: PMC2581815  PMID: 18602657
15.  Immediate and Delayed Effects of Word Frequency and Word Length on Eye Movements in Reading: A Reversed Delayed Effect of Word Length 
Three experiments examined the effects in sentence reading of varying the frequency and length of an adjective on (a) fixations on the adjective and (b) fixations on the following noun. The gaze duration on the adjective was longer for low frequency than for high frequency adjectives and longer for long adjectives than for short adjectives. This contrasted with the spillover effects: Gaze durations on the noun were longer when adjectives were low frequency but were actually shorter when the adjectives were long. The latter effect, which seems anomalous, can be explained by three mechanisms: (a) Fixations on the noun are less optimal after short adjectives because of less optimal targeting; (b) shorter adjectives are more difficult to process because they have more neighbors; and (c) prior fixations before skips are less advantageous places to extract parafoveal information. The viability of these hypotheses as explanations of this reverse length effect on the noun was examined in simulations using an updated version of the E-Z Reader model
doi:10.1037/0096-1523.34.3.726
PMCID: PMC2715992  PMID: 18505334
reading; eye movements; attention; models; E-Z Reader
16.  Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma 
PPAR Research  2009;2010:848645.
Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.
doi:10.1155/2010/848645
PMCID: PMC2712952  PMID: 19639032
17.  Principles of Modular Tumor Therapy 
Cancer Microenvironment  2009;2(Suppl 1):227-237.
Nature is interwoven with communication and is represented and reproduced through communication acts. The central question is how may multimodal modularly acting and less toxic therapy approaches, defined as modular therapies, induce an objective response or even a continuous complete remission, although single stimulatory or inhibitingly acting drugs neither exert mono-activity in the respective metastatic tumor type nor are they directed to potentially ‘tumor-specific’ targets. Modularity in the present context is a formal pragmatic communicative systems concept, describing the degree to which systems objects (cells, pathways etc.) may be communicatively separated in a virtual continuum, and recombined and rededicated to alter validity and denotation of communication processes in the tumor. Intentional knowledge, discharging in reductionist therapies, disregards the risk-absorbing background knowledge of the tumor’s living world including the holistic communication processes, which we rely on in every therapy. At first, this knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. All communication-relevant steps, such as intentions, understandings, and the appreciation of messages, may be modulated simultaneously, even with a high grade of specificity. Thus, modular therapy approaches including risk-absorbing and validity-modifying background knowledge may overcome reductionist idealizations. Modular therapies show modular events assembled by the tumor’s living world as an additional evolution-constituting dimension. This way, modular knowledge may be acquired from the environment, either incidentally or constitutionally. The new communicatively defined modular coherency of environment, i.e. the tumor-associated microenvironment, and tumor cells open novel ways for the scientific community in ‘translational medicine’.
doi:10.1007/s12307-009-0023-x
PMCID: PMC2756340  PMID: 19593676
Evolution; Inflammation; Metastatic tumor; Personalized therapy; Systems assessment tools; Systems biology
19.  Systems Biology: A Therapeutic Target for Tumor Therapy 
Cancer Microenvironment  2008;1(1):159-170.
Tumor-related activities that seem to be operationally induced by the division of function, such as inflammation, neoangiogenesis, Warburg effect, immune response, extracellular matrix remodeling, cell proliferation rate, apoptosis, coagulation effects, present itself from a systems perspective as an enhancement of complexity. We hypothesized, that tumor systems-directed therapies might have the capability to use aggregated action effects, as adjustable sizes to therapeutically modulate the tumor systems’ stability, homeostasis, and robustness. We performed a retrospective analysis of recently published data on 224 patients with advanced and heavily pre-treated (10% to 63%) vascular sarcoma, melanoma, renal clear cell, cholangiocellular, carcinoma, hormone-refractory prostate cancer, and multivisceral Langerhans’ cell histiocytosis enrolled in nine multi-center phase II trials (11 centers). Each patient received a multi-targeted systems-directed therapy that consisted of metronomic low-dose chemotherapy, a COX-2 inhibitor, combined with one or two transcription modulators, pioglitazone +/− dexamethasone or IFN-alpha. These treatment schedules may attenuate the metastatic potential, tumor-associated inflammation, may exert site-specific activities, and induce long-term disease stabilization followed by prolonged objective response (3% to 48%) despite poor monoactivity of the respective drugs. Progression-free survival data are comparable with those of reductionist-designed standard first-line therapies. The differential response patterns indicate the therapies’ systems biological activity. Understanding systems biology as adjustable size may break through the barrier of complex tumor-stroma-interactions in a therapeutically relevant way: Comparatively high efficacy at moderate toxicity. Structured systems-directed therapies in metastatic cancer may get a source for detecting the topology of tumor-associated complex aggregated action effects as adjustable sizes available for targeted biomodulatory therapies.
doi:10.1007/s12307-008-0012-5
PMCID: PMC2654356  PMID: 19308694
Systems biology; Tumor microenvironment; Transcription factors; Pioglitazone; PPARs; Dexamethasone; Interferon-alpha; COX-2 inhibitor; Metronomic low dose chemotherapy
20.  Enantioselective Synthesis of α-tertiary Hydroxyaldehydes by Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates 
Chiral α-tertiary hydroxyaldehydes are very versatile building blocks in synthetic chemistry. Herein, we reported the first examples of a catalytic asymmetric protocol for the synthesis of such compounds from readily available α-halo or α-hydroxy ketones or enol silyl ethers with excellent yields and enantioselectivity. Its synthetic utility is demonstrated in the short, efficient formal synthesis of (S)-oxybutynin. In this process, the chiral ligand controls with the regioselectivity as well as enantioselectivity.
doi:10.1021/ja067342a
PMCID: PMC2533583  PMID: 17212401
21.  C-reactive Protein in Patients with Metastatic Clear Cell Renal Carcinoma: An Important Biomarker for Tumor-associated Inflammation 
Biomarker Insights  2007;1:87-98.
Two consecutive multi-center phase II trials were designed to prove the hypothesis, whether therapeutic modeling of tumor-associated inflammatory processes could result in improved tumor response.
Therapy in both trials consisted of low-dose capecitabine 1g/m2 twice daily p.o. for 14 days, every 3 weeks, day 1+, and rofecoxib 25 mg daily p.o., day 1+ (from 11/04 etoricoxib 60 mg daily instead) plus pioglitazone 60 mg daily p.o., day 1+. In study II low-dose IFN-α 4.5 MU sc. three times a week, week 1+, was added until disease progression.
Eighteen, and 33 patients, respectively, with clear cell renal carcinoma and progressive disease were enrolled. Objective response (48%) was exclusively observed in study II (PR 35%, CR 13%), and paralleled by a strong CRP response after 4 weeks on treatment, p = 0.0005, in all 29 pts (100%) with elevated CRP levels. Median progression-free survival could be more than doubled from a median of 4.7 months (95% CI, 1.0 to 10.4) to 11.5 months (6.8 to 16.2) in study II, p = 0.00001. Median overall survival of population II was 26 months.
Efficacious negative regulation of tumor-associated inflammation by transcription modulators may result in a steep increase of tumor response and survival.
PMCID: PMC2716790  PMID: 19690640
Anti-inflammatory therapy; Interferon-alpha; PPARgamma; COX-2
22.  Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer 
Molecular Pathology  2003;56(5):286-292.
Aims: To evaluate the usefulness of molecular markers in predicting histopathological and clinical response to preoperative high dose chemotherapy (HDCT) and survival of patients with advanced gastric cancer.
Methods: In a phase II trial, 25 patients with metastatic gastric cancer received preoperative tandem HDCT consisting of etoposide, cisplatin, and mitomycin, followed by autologous bone marrow transplantation to achieve surgical resectability. Samples before and after treatment, from normal and tumour tissue, were characterised histopathologically, and both p53 and BAX expression was analysed by immunohistochemistry. Pretreatment formalin fixed, paraffin wax embedded samples from normal and tumour tissue were microdissected, and the extracted DNA was preamplified using improved primer extension preamplification polymerase chain reaction. Detection of microsatellite instability (MSI) or loss of heterozygosity (LOH) was performed using markers for p53, BAX, BAT25, BAT26, D2S123, D17S250, and APC. Exons 5–9 of the p53 gene were sequenced directly on ABI 373.
Results: Four parameters were significantly associated with response to chemotherapy and prolonged overall survival: positive p53 immunostaining, positive p53 mutation status before chemotherapy, strong histological regression induced by preoperative HDCT, and surgical treatment. Patients’s sex or age, tumour location or stage, lymph node status, Lauren classification, MSI, or LOH did not influence duration of survival significantly in this high risk population.
Conclusion: Positive p53 immunostaining and p53 mutation status in pretreatment tumour biopsies might be useful molecular predictors of response and prognosis in patients with advanced gastric cancer treated by preoperative HDCT.
PMCID: PMC1187340  PMID: 14514923
gastric cancer; preoperative high dose chemotherapy; molecular parameters; histological regression; p53
23.  QOI2/356: Trying to Meet the User's Needs in A Web-based Patient Information System 
Introduction
In 1997, a new German Web-based patient information system (www.therapie.net) was developed. As a knowledge base, systematic reviews of the effectiveness of health technologies were used. Widely accepted and additional features were introduced into the system in order to gain a high quality product.
Methods
At the start of the project, text-based patient information was simply converted into HTML format. In the next step, the HON Code principles for medical and health Web sites were implemented. Although the resulting Web pages followed these principles, they were not very user friendly. To improve this deficit all the information available in the system was restructured into main information units. These units determined the basic structure of the information system. Furthermore, the original patient information texts were structured into several divisions and subdivisions, say information levels. This process resulted in a large number of clear text-blocks, each of which showed a branched text navigation bar as well as the content itself.
Results
Merging different solutions for user interfaces and web design, the system was developed on the basis of the frame technique. The implementation of frames facilitates a constant system environment. A system navigation bar is throughout present at the top of the page. It allows the direct and quick access of a specific part of the system -- e.g. introduction, topics, contact, glossary, imprint. Accessing a specific topic, a text navigation bar appears in a left frame. The navigation bars allow the direct selection of the needed information and give a clear message about the user's location in the information space. The different text blocks and system parts are connected through hyperlinks. To avoid confusion, while the user is following such links, another smaller browser window is opened where appropriate. Thus, for example, if a user comes upon a medical term, which is described in the glossary, he can just click on the word and read its description in the smaller window without leaving the original text.
Discussion
A lot of patient information sites in the World Wide Web seem to show a good quality of content, but are lacking user friendliness, and vice versa. To combine these two features, we introduced the widely accepted quality principles of the HON code and developed some own principles, which we presumed to meet the user's needs. However, the techniques and possibilities of the web are changing and developing rapidly. Consequently, all providers of web-based patient information will have to be in pace with this development to ensure the high quality of their products. An online survey (starting in May 1999) will be used to evaluate the quality of our approach.
doi:10.2196/jmir.1.suppl1.e96
PMCID: PMC1761826
Patient Participation; Evidence-Based Medicine; Quality Control; Public Health; Internet
24.  Association of hand and knee osteoarthritis: evidence for a polyarticular disease subset. 
OBJECTIVE--To examine the association between hand and knee osteoarthritis (OA) in a community based population. METHODS--Radiographs of 695 participants aged > or = 40 years in the Baltimore Longitudinal Study of Aging were read for changes of OA, using Kellgren-Lawrence grade > or = 2 as the case definition. RESULTS--Logistic regression analyses, adjusting for age, gender and body mass index, revealed a significant association between OA in the knee and the following joint groups: distal and proximal interphalangeal (DIP, PIP) and Hand2 (OA in two or more hand joint groups) for grade 2-4 and grade 3-4 disease, and the first carpometacarpal (CMC1) joint for grade 3-4 disease. CONCLUSION--There is an association between OA in hand sites and the knee. The strength of the associations increases with increasing disease severity. For the PIP site, there is a trend toward increasing strength of association for increasing numbers of affected joints and bilateral disease.
PMCID: PMC1010077  PMID: 8572729
25.  Variant and invariant high-probability requests: increasing appropriate behaviors in children with emotional-behavioral disorders. 
This study examined the effects of variant versus invariant high-probability (high-p) request sequences on the performance of requests to initiate a social bid by young children with emotional-behavioral disorders. In the initial phases of the investigation, a multiple baseline design showed that the delivery of invariant sequences (i.e., high-p requests delivered in the same sequence) produced initial increases in compliance to requests to initiate a social bid to a peer. However, increases were not maintained across the invariant condition. The delivery of variant high-p sequences produced increases in compliance to requests to initiate social bids that were maintained across the variant condition. In a follow-up condition, the number of requests within the pool of the variant and invariant high-p requests were controlled. Results of the follow-up condition replicated those found in the initial condition. Implications for applied use and future research are discussed.
doi:10.1901/jaba.1996.29-471
PMCID: PMC1284004  PMID: 8995830

Results 1-25 (29)