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PubMed2000

Four structural risk factors identify most fibril-forming kappa light chains.

Antibody light chains (LCs) comprise the most structurally diverse family of proteins involved in amyloidosis. Many antibody LCs incorporate structural features that impair their stability and solubility, leading to their assembly into fibrils and to their subsequent pathological deposition when produced in excess during multiple myeloma and primary amyloidosis. The particular amino acid variations in antibody LCs that account for fibril formation and amyloidogenesis have not been identified. This study focuses on amyloidogenesis within the kappa1 family of human LCs. Reanalysis of the current database of primary structures of proteins from more than 100 patients who produced kappa1 LCs, 37 of which were amyloidogenic, reveals apparent structural features that may contribute to amyloidosis. These features include loss of conserved residues or the gain of particular residues through mutation at sites involving a repertoire of approximately 20% of the amino acid positions in the light chain variable domain (V(L)). Moreover 80% of all kappa1 amyloidogenic V(L)s are identifiable by the presence of at least one of three single-site substitutions or the acquisition of an N-linked glycosylation site through mutations. These findings suggest that it is feasible to predict fibril propensity by analysis of primary structure.

Alzheimer Disease↗
PubMed1995

X-linked retinitis pigmentosa: re-evaluation of fundus findings and the use of haplotype analysis in clarification of carrier female status.

The identification by fundus examination of those females carrying an X-linked retinitis pigmentosa (RP) gene can reportedly be as high as 87%. In genetic counselling sessions with young females with a 50% risk of being a carrier who wished to know their status, it has not been possible to achieve such a level of success. A review and reanalysis of previous reports indicated that if a tapetal-like reflex was not present in those age 35 years or less, the likelihood of identifying a carrier by fundus examination was small. A family with 7 females with a 50% risk of being a carrier of X-linked RP was evaluated using haplotype analysis in an attempt to identify the X chromosome carrying the RP gene. In the family described, it was possible to establish that a mutation in the RP3 locus most likely causes the disease. This has permitted the determination of the carrier status in each of the females with a high degree of certainty.

Adolescent↗
PubMed2006

External quality assessment of HbA(1c) for point of care testing.

OBJECTIVES: To evaluate the long term total imprecision of HbA(1c) testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) < 3% for HbA(1c) and to study the cost of an external quality assurance program for point-of-care HbA(1c) The county uses Bayer DCA 2000 for point-of-care HbA(1c) testing currently having 23 of these instruments. METHODS: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA(1c) testing. The samples were first analysed on a Bayer DCA 2000 and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II, Biorad). The testing was performed approximately 8 times per year with each instrument. RESULTS: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%. CONCLUSION: The DCA 2000 systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.

Calibration↗
PubMed2005

Within-day feeding behavior of lactating dairy cows measured using a real-time control system.

The suitability of a statistical model for describing within-day feeding behavior, and potential relationships between model parameters and commonly measured experimental variables were examined. Forty multiparous, midlactation Holstein cows were fed using a real-time control system to record the date of each visit to a feeder, entrance time, exit time, and feed consumed over a 6-wk period. Daily feed consumption, number of visits, meal duration, and within-visit rate of food intake were then calculated. Two peaks in within-day rates of feed intake were indicated, suggesting that feeding activity was randomly distributed around each peak, that is, binormal. Parameters describing the distributions (means, standard deviations, and the percentage of total feeding activity associated with each peak) were estimated. An adjusted average of 91% of the variation in within-day feeding activity was explained by the binormal model. Relationships between model parameters and commonly measured experimental variables were also identified; behavioral traits were correlated with total feed intake. Feeding activity patterns in literature data were also amenable to reanalysis by the binormal model. Lactating cows consistently exhibited a distinct diurnal pattern in feeding activity; they were most active near sunrise and again near sunset (crepuscular). Effects of various management operations (e.g., feeding and milking times and frequencies, and lighting) on within-day feeding patterns remain to be established, although a statistical model for evaluating them is now available. The patterns may have important implications for scheduling management activities to maximize feed intake and production.

Animal Feed↗
PubMed1977

Brain-tumor therapy. Quantitative analysis using a model system.

A recently developed colony-formation assay has been used to evaluate in vivo 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy of a transplantable rat brain-tumor model. A comparison of the in vitro colony-forming capacity of treated and untreated tumor cells permits calculation of the fraction of clonogenic tumor cells surviving in vivo therapy; The plateau that we previously observed o the BCNU dose-response curve is not the result of repair of potentially lethal damage, since no change in the 0.1% of surviving clonogenic tumor cells occurs during the first 2 to 4 days after treatment. Although reanalysis of the dose-response curve indicates that sublethal damage exists, its repair is probably minimal. The most likely explanation for the observed limitation of the BCNU effect is the drug's failure to reach all clonogenic cells. A dose of BCNU that kills more than 99.9% of clonogenic tumor cells within 30 minutes of treatment results in only a 60% decrease in tumor weight by Day 14. This disparity is explained by retarded removal of dead cells, and, along with a previously determined 90% cell-kill threshold necessary to appreciate increased animal survival, demonstrates the inherent limitations of measurements of tumor size (including brain scans and clinical patient evaluations) in evaluating the efficacy of brain-tumor therapy. Following at LD10 dose of BCNU the surviving clonogenic tumor cells increase in number after latency period of 2 to 4 days; during regrowth the cell doubling time is 40 hours. Marked variability in tumor response and regrowth was noted. The determination of information regarding disturbed tumor cell kinetics and tumor heterogeneityis essential for the proper planning of combination chemotherapy and multimodality regimens.

Animals↗
PubMed2006

Gender discrimination may be worse than you think: testing ordinal interactions in power research.

The authors reanalyze the data of a study by S. M. Elias and R. J. Loomis (2004), which aimed to determine how an instructor's gender may influence his or her ability to gain student compliance. S. M. Elias and R. J. Loomis observed few significant gender effects using traditional multivariate analyses of variance. The authors reanalyze this data using the more appropriate statistical techniques for detecting ordinal interactions recommended by M. J. Strube and P. Bobko (1989) and S. M. Elias (2004). An ordinal interaction occurs when 1 cell of a 2 x 2 design is responsible for a significant interaction (e.g., female instructors suffering only when rated by male students). Reanalysis of the data resulted in more robust findings.

Adolescent↗
PubMed2006

The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease.

OBJECTIVES: To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to moderately severe Alzheimer's disease (AD) and of memantine for moderately severe to severe AD. DATA SOURCES: Electronic databases, experts in the field and manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE). REVIEW METHODS: A systematic review of the literature and an economic evaluation were undertaken. The quality of included randomised controlled trials (RCTs) was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. An outline assessment of economic evaluations was undertaken using a standard checklist. The clinical and cost-effectiveness data were synthesised through a narrative review with full tabulation of the results of included studies. Where appropriate, meta-analysis of data was undertaken. RESULTS: For mild to moderately severe AD, the results of the study suggested that all three treatments were beneficial when assessed using cognitive outcome measures. Global outcome measures were positive for donepezil and rivastigmine, but mixed for galantamine. Results for measures of function were mixed for donepezil and rivastigmine, but positive for galantamine. Behaviour and mood measures were mixed for donepezil and galantamine, but showed no benefit for rivastigmine. For memantine, two published RCTs were included; in one of these trials the participants were already being treated with donepezil. The results suggest that memantine is beneficial when assessed using functional and global measurements. The effect of memantine on cognitive and behaviour and mood outcomes is, however, less clear. Literature on the cost-effectiveness of donepezil, rivastigmine and galantamine was dominated by industry-sponsored studies, and studies varied in methods and results. Of the three UK studies, two report donepezil as not cost-effective, whereas a third study reports an additional cost (1996 pounds sterling) of between 1200 pounds sterling and 7000 pounds sterling per year in a non-severe AD health state (concerns over these estimates are raised, suggesting that they may underestimate the true cost-effectiveness of donepezil). Cost-effectiveness analysis undertaken in this review suggests that donepezil treatment has a cost per quality-adjusted life-year (QALY) in excess of 80,000 pounds sterling, with donepezil treatment reducing the mean time spent in full-time care (delays progression of AD) by 1.42-1.59 months (over a 5-year period). From four published cost-effectiveness studies, two UK studies report additional costs associated with rivastigmine treatment. Cost-effectiveness analysis undertaken in the current review suggests that rivastigmine treatment has a cost per QALY in excess of 57,000 pounds sterling, with rivastigmine treatment reducing the mean time spent in full-time care (delays progression) by 1.43-1.63 months (over a 5-year period). From five published cost-effectiveness studies, one UK study reports a cost per QALY of 8693 pounds sterling for 16-mg galantamine treatment and 10,051 pounds sterling for 24-mg galantamine treatment (concerns raised suggest that this may underestimate the true cost-effectiveness of galantamine). Cost-effectiveness analysis undertaken in the present review suggests that galantamine treatment has a cost per QALY in excess of 68,000 pounds sterling, with galantamine reducing the time spent in full-time care (delays progression) by 1.42-1.73 months (over a 5-year period). From two published cost-effectiveness studies, one reports analysis for the UK, finding that memantine treatment results in cost savings and benefits in terms of delaying disease progression (concerns raised suggest that this may underestimate the true cost-effectiveness of memantine). In the current review, the cost-effectiveness of memantine has not been modelled separately, but where alternative parameter inputs on the cost structure and utility values have been used in a reanalysis using the industry model, the cost-effectiveness is reported at between 37,000 pounds sterling and 52,000 pounds sterling per QALY, with this alternative analysis still based on what is regarded as an optimistic or favourable effectiveness profile for memantine. CONCLUSIONS: Although results from the clinical effectiveness review suggest that these treatments may be beneficial, a number of issues need to be considered when assessing the results of the present review, such as the characteristics of the participants included in the individual trials, the outcome measures used, the length of study duration, the effects of attrition and the relationship between statistical significance and clinical significance. Many included trials were sponsored by industry. For donepezil, rivastigmine and galantamine, the cost savings associated with reducing the mean time spent in full-time care do not offset the cost of treatment sufficiently to bring estimated cost-effectiveness to levels generally considered acceptable by NHS policy makers. It is difficult to draw conclusions on the cost-effectiveness of memantine; it is suggested that further amendments to the potentially optimistic industry model (measure of effect) would offer higher cost per QALY estimates. Future research should include: information on the quality of the outcome measures used; development of quality of life instruments for patients and carers; studies assessing the effects of these interventions of durations longer than 12 months; comparisons of benefits between interventions; and research on the prediction of disease progression.

Aged↗
PubMed2004

The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis.

OBJECTIVES: To address the structural issues relating to mortality and quality of life (QoL) effects and to identify data on the general pattern of QoL of rheumatoid arthritis (RA) patients through a restructured and enhanced version of the Birmingham Preliminary Model (BPM). DATA SOURCES: Electronic databases and a postal survey of current UK rheumatological practice. REVIEW METHODS: The focus for this report was to evaluate two new drugs, etanercept and infliximab [antibodies against tumour necrosis factor (anti-TNFs)], for use in the treatment of RA using the Birmingham Rheumatoid Arthritis Model (BRAM). Having carried out a rapid systematic review of physician surveys of current disease-modifying antirheumatic drugs (DMARDs) usage patterns in adult patients with RA and a postal survey of consultant rheumatologists working in the UK, the drug sequences were then identified for the model. A series of analyses were then run using the model. The issue of specifying the correct comparison in the analysis being undertaken was investigated using two separate analyses: the situation of comparing anti-TNFs with placebo, and the comparison of a sequence using anti-TNFs with a sequence that represents current practice in the UK. RESULTS: Results from the survey of rheumatologists highlighted the fact that RA has different manifestations and responds to different agents in different patients, all of which makes any summary of practice difficult to achieve and open to the criticism of being an oversimplification. However, the findings generally agree with other surveys and trends observed, such as the increasing acceptance of methotrexate as first line drug of choice in patients with RA, especially if the disease is of an aggressive nature. The newer anti-TNF agents have also begun to be incorporated into use. The incremental cost-effectiveness ratios resulting from the use of an inappropriate comparator of placebo were consistently lower than in the base case where appropriate comparator drugs sequences are used. The focus of the BRAM on a drug sequence helped to avoid the incremental cost-effectiveness of new treatments appearing lower than they really are when inappropriate comparators are used. To test the effect on the analysis results of using the disease-modifying antirheumatic sequence that represents current UK practice, the BRAM was run for the strategies representing current UK practice. The results were not very different from the base-case results. CONCLUSIONS: The main achievement of this work was to bring about a more realistic modelling of real-life clinical pathways and events, as it has developed from the BPM to the BRAM. This has been brought about by overcoming structural and data limitations. In addition, the modelling approach reflected in the BRAM is applicable to other chronic conditions, especially those where a sequential approach to therapeutic options exists. The model has been successfully restructured so that different sequences of treatment can readily be considered, including the sequence that best represents current clinical practice in the UK. In addition, the flexibility inherent in using a modelling approach to consider these health policy questions has been demonstrated. One of the key uncertainties that can now be explored concerns the impact of new drugs on disease progression. Current evidence on this is weak, but should new agents demonstrate such a benefit then the BRAM may be a suitable vehicle through which to investigate the costs and full effects. Inevitably, there remain problems and limitations with the BRAM, but these are almost entirely data limitations. As data on these issues become available the BRAM provides a convenient tool through which reanalysis might be undertaken.

Adolescent↗
PubMed2005

Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation.

OBJECTIVES: To determine whether laparoscopic methods are more effective and cost-effective than open mesh methods of inguinal hernia repair, and then whether laparoscopic transabdominal preperitoneal (TAPP) repair is more effective and cost-effective than laparoscopic totally extraperitoneal (TEP). DATA SOURCES: Electronic databases. Conference proceedings. Manufacturers' submissions to the National Institute for Clinical Excellence (NICE) were reviewed. REVIEW METHODS: Selected studies were rigorously assessed. Dichotomous outcome data were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Time to return to usual activities was described using hazard ratios derived from individual patient data reanalysis. A review of economic evaluations undertaken by NICE in 2001 was updated and an economic evaluation was performed. The estimation of cost-effectiveness focused on the comparison of laparoscopic repair with open flat mesh. A Markov model incorporating the data from the systematic review was used to estimate cost-effectiveness for a time horizon up to 25 years. RESULTS: Thirty-seven randomised control trials (RCTs) and quasi-RCTs met the inclusion criteria on effectiveness. Fourteen studies were included in the review of economic evaluations. Laparoscopic repair was associated with a faster return to usual activities and less persisting pain and numbness. There also appeared to be fewer cases of wound/superficial infection and haematoma. However, operation times are longer and there appears to be a higher rate of serious complications in respect of visceral (especially bladder) injuries. Mesh infection is very uncommon with similar rates noted between the surgical approaches. There is no apparent difference in the rate of hernia recurrence. Laparoscopic repair was more costly to the health service than open repair, with an estimated extra cost from studies conducted in the UK of about 300-350 pounds per patient. The point estimates of cost provided by the economic model also suggest that the laparoscopic techniques are more costly (approximately 100-200 pounds more per patient after 5 years). From the review of economic evaluations, the estimates of incremental cost per additional day at usual activities were between 86 pounds and 130 pounds. Where productivity costs were included, they eliminated the cost differential between laparoscopic and open repair. Additional analysis incorporating new trial evidence suggested that TEP was associated with significantly more recurrences than open mesh but these data did not greatly influence cost-effectiveness. CONCLUSIONS: For the management of unilateral hernias, the base-case analysis and most of the sensitivity analysis suggest that open flat mesh is the least costly option but provides less quality adjusted life years (QALYs) than TEP or TAPP. TEP is likely to dominate TAPP (on average TEP is estimated to be less costly and more effective). It is likely that, for management of symptomatic bilateral hernias, laparoscopic repair would be more cost-effective as differences in operation time (a key cost driver) may be reduced and differences in convalescence time are more marked (hence QALYs will increase) for laparoscopic compared with open mesh repair. When possible repair of contralateral occult hernias is taken into account, TEP repair is most likely to be considered cost-effective at threshold values for the cost per additional QALY above 20,000 pounds. The increased adoption of laparoscopic techniques may allow patients to return to usual activities faster. This may, for some people, reduce any loss of income. For the NHS, increased use of laparoscopic repair would lead to an increased requirement for training and the risk of serious complications may be higher. Chronic pain should now be addressed prospectively using standard definitions and allowing assessment of the degree of pain. More evidence is required on the loss of utility caused by persisting pain and numbness, as well as serious complications resulting from minor surgery. Prospective population-based registries of new surgical procedures may be the best way to address this, as a complement to randomised trials assessing effectiveness. Further research relating to whether the balance of advantages and disadvantages changes when hernias are recurrent or bilateral is also required as current data are limited. Methodologically sound RCTs are needed to consider the relative merits and risks of TAPP and TEP. Further methodological research is required into the complexity of laparoscopic groin hernia repair and the improvement of performance that accompanies experience.

Cost-Benefit Analysis↗
PubMed2005

A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis.

OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of selective oestrogen receptor modulators, bisphosphonates and parathyroid hormone (subject to licensing) for the prevention and treatment of osteoporosis and the prevention of osteoporotic fractures in postmenopausal women. DATA SOURCES: Electronic databases. REVIEW METHODS: Studies that met the review's entry criteria were eligible for inclusion in the meta-analyses provided that they reported fracture incidence in terms of the number of patients suffering fractures. Meta-analysis was carried out using the random-effects model. A model was constructed to estimate the cost-effectiveness of osteoporosis interventions. The model calculated the number of fractures that occurred and provided the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs). In addition, the conditions of breast cancer and coronary heart disease (CHD) were modelled, as some interventions have been shown to affect the risk of these conditions. RESULTS: Ninety randomised controlled trials (RCTs) met the inclusion criteria. They related to the five interventions (alendronate, etidronate, risedronate, raloxifene and teriparatide) and to five comparators (calcium, calcium plus vitamin D, calcitriol, hormone replacement therapy and exercise), as well as placebo or no treatment. All five interventions have been shown to reduce the risk of vertebral fracture in women with severe osteoporosis with adequate calcium intakes. However, none of these drugs has been demonstrated, by direct comparison, to be significantly more effective than either each other or the other active interventions reviewed in this report. The intervention costs of treating all osteoporotic women, for a period of 5 years, were in the region of pound 900-1500 million for alendronate, etidronate, risedronate and raloxifene. The cost per QALY ratios fell dramatically with age. Assuming the risks of a woman with severe osteoporosis at the threshold of osteoporosis, no treatment had a cost per QALY below pound 35,000 at 50 years of age. At 60 years of age, the cost per QALY of raloxifene was pound 26,000 assuming no impact on hip fractures, and pound 31,000 assuming an adverse effect. However, these results are driven by the effect on breast cancer and the assumptions made regarding this disease state. No other intervention had a cost per QALY below pound 35,000. When analyses were conducted assuming that the fracture risk is doubled at each site, alendronate and risedronate had cost per QALY ratios below pound 30,000 at all ages. For women at the threshold of osteoporosis, without a prior fracture and aged 70 years, the cost per QALY of the three bisphosphonates ranged from pound 34,000 to pound 41,000. Raloxifene had a cost per QALY of pound 23,000, assuming no effect on hip fracture, given assumptions regarding breast cancer. At 80 years of age, the cost per QALY of alendronate and risedronate was below pound 20,000. This was true for etidronate when incorporating observational data, but the value rose to pound 69,000 when only RCT data were used. No other intervention had a cost per QALY below pound 35,000. It was assumed that doubling the risk of fracture for women without a prior fracture would give results similar to patients at the threshold of osteoporosis with a prior fracture. CONCLUSIONS: Of the five interventions, only raloxifene appeared to reduce the risk of vertebral fracture in postmenopausal women unselected for low bone mineral density (BMD). However, as the full data have not been made public, there is some uncertainty regarding this result. None of the five interventions has been shown to reduce the risk of non-vertebral fracture in women unselected for low BMD. All of the proposed interventions provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the age of the patient. The estimated costs varied widely for the interventions. These net costs were markedly different by age, with some interventions becoming cost-saving at higher age ranges in patients with a prior fracture. Areas for future research include: the evidence base for the efficacy of fracture prevention in the very elderly, reanalysis of raloxifene using a dedicated breast cancer and CHD model, and more trials considering the cost-effectiveness of teriparatide.

Age Factors↗
PubMed2003

[Molecular and quantitative analyses of Malassezia microflora on the skin of atopic dermatitis patients and genotyping of M. globosa DNA].

To elucidate the role of Malassezia species in atopic dermatitis (AD) requires investigation of the Malassezia microflora on the skin of AD patients. Previously, M. furfur was considered the dominant species in the microflora, however, this microorganism has been reclassified into five species and reanalysis of the microflora based on the current Malassezia taxonomy is therefore needed. Malassezia is more difficult to isolate and culture than other pathogenic yeasts such as Candida and Cryptococcus, making it difficult to elucidate the microflora of AD patients accurately. We developed a PCR-based non-culture method that does not require the use of isolation or culture techniques. Of the members of the genus Malassezia, M. globosa colonized the skin of both AD patients and healthy subjects more frequently than other Malassezia species. In addition, we found polymorphisms in the intergenic spacer 1 region of the M. globosar RNA gene. The genotypes of the microorganisms obtained from AD patients were significantly different from those obtained from healthy subjects. We believe that a specific genotype of M. globosa is responsible for exacerbation of AD.

DNA, Fungal↗
PubMed2026

A High-Resolution Stereo-Seq Spatial Transcriptomic Resource for Adult Holstein Cattle Liver.

The bovine liver is a highly compartmentalized organ that plays essential roles in continuous gluconeogenesis and nitrogen recycling; however, its spatial molecular architecture has remained largely uncharacterized due to the limitations of traditional bulk and single-cell approaches. To address this gap, Spatial Enhanced Resolution Omics-sequencing (Stereo-seq) was utilized to generate a subcellular-resolution (500 nm) transcriptomic map of an adult Holstein cattle liver, and a refined reference-guided workflow was implemented to overcome standard annotation limitations in livestock. Raw sequencing data were processed using the Stereo-seq Analysis Workflow and analyzed with Stereopy, Seurat, SingleR, and reference-guided workflows. Spatial aggregation was evaluated at Bin20, Bin50, Bin100, Bin150, and Bin200. Increasing bin size increased molecular identifier counts and detected-gene complexity while progressively reducing spatial granularity. Bin50, corresponding to 50 &#xd7; 50 DNA nanoballs and an approximate nominal footprint of 25 &#xd7; 25 &#xb5;m, was therefore selected as a practical intermediate aggregation level for the primary analyses. Quality-control assessment, Leiden clustering, UMAP visualization, reference-based cell-type annotation, cluster-marker analysis, and spatial mapping of canonical hepatic genes demonstrated preservation of biologically interpretable liver transcriptional organization. Raw sequencing data processed spatial matrices, annotated objects, and analysis code are publicly available to support reanalysis and computational benchmarking. In summary, we present a Stereo-seq spatial transcriptomic resource generated from liver tissue of an adult Holstein cow. This initial resource provides a valuable foundation for future studies of bovine liver biology, comparative genomics, and the spatial basis of livestock health and production traits.

Animals↗
PubMed2005

The Chemnitz LogAnalyzer: a tool for analyzing data from hypertext navigation research.

Computer-based studies usually produce log files as raw data. These data cannot be analyzed adequately with conventional statistical software. The Chemnitz LogAnalyzer provides tools for quick and comfortable visualization and analyses of hypertext navigation behavior by individual users and for aggregated data. In addition, it supports analogous analyses of questionnaire data and reanalysis with respect to several predefined orders of nodes of the same hypertext. As an illustration of how to use the Chemnitz LogAnalyzer, we give an account of one study on learning with hypertext. Participants either searched for specific details or read a hypertext document to familiarize themselves with its content. The tool helped identify navigation strategies affected by these two processing goals and provided comparisons, for example, of processing times and visited sites. Altogether, the Chemnitz LogAnalyzer fills the gap between log files as raw data of Web-based studies and conventional statistical software.

Adult↗
PubMed2004

Probability matching, accuracy maximization, and a test of the optimal classifier's independence assumption in perceptual categorization.

Observers completed perceptual categorization tasks that included 25 base-rate/payoff conditions constructed from the factorial combination of five base-rate ratios (1:3, 1:2, 1:1, 2:1, and 3:1) with five payoff ratios (1:3, 1:2, 1:1, 2:1, and 3:1). This large database allowed an initial comparison of the competition between reward and accuracy maximization (COBRA) hypothesis with a competition between reward maximization and probability matching (COBRM) hypothesis, and an extensive and critical comparison of the flat-maxima hypothesis with the independence assumption of the optimal classifier. Model-based instantiations of the COBRA and COBRM hypotheses provided good accounts of the data, but there was a consistent advantage for the COBRM instantiation early in learning and for the COBRA instantiation later in learning. This pattern held in the present study and in a reanalysis of Bohil and Maddox (2003). Strong support was obtained for the flat-maxima hypothesis over the independence assumption, especially as the observers gained experience with the task. Model parameters indicated that observers' reward-maximizing decision criterion rapidly approaches the optimal value and that more weight is placed on accuracy maximization in separate base-rate/payoff conditions than in simultaneous base-rate/payoff conditions. The superiority of the flat-maxima hypothesis suggests that violations of the independence assumption are to be expected, and are well captured by the flat-maxima hypothesis, with no need for any additional assumptions.

Decision Making↗
PubMed2004

Gender and lexical access in Bulgarian.

Two procedures were used to explore the effects of semantic and grammatical gender on the recognition and processing of Bulgarian nouns, in relation to other factors that are known to affect lexical access. This study in a three-gender language was modeled on previous work in Italian, a two-gender language (Bates, Devescovi, Pizzamiglio, D'Amico, & Hernandez, 1995). Words were presented auditorily in randomized lists in two tasks: (1) repeat the word as quickly as possible and (2) determine the grammatical gender of the noun as soon as possible and indicate the decision by pressing a button. Reaction times in both tasks were influenced by phonological factors, word frequency, and irregularity of gender marking, but semantic and grammatical gender affected only gender monitoring. The significant contribution of semantic gender to processing in Bulgarian contrasts with previous findings for Italian. Also, we obtained an interaction between sex of the subject and noun gender, reflecting a bias toward one's own grammatical gender "counterpart" (especially for females). Reanalysis of the prior study in Italian showed a similar interaction but confirmed no effects of the semantic gender of the noun, suggesting that these two natural gender effects can dissociate. Possible reasons for cross-linguistic differences are discussed, with implications for comparative studies of gender and lexical access.

Adolescent↗
PubMed2004

Cultural life scripts structure recall from autobiographical memory.

Three classes of evidence demonstrate the existence of life scripts, or culturally shared representations of the timing of major transitional life events. First, a reanalysis of earlier studies on age norms shows an increase in the number of transitional events between the ages of 15 and 30 years, and these events are associated with narrower age ranges and more positive emotion than events outside this period. Second, 1,485 Danes estimated how old hypothetical centenarians were when they had been happiest, saddest, most afraid, most in love, and had their most important and most traumatic experiences. Only the number of positive events showed an increase between the ages of 15 and 30 years. Third, undergraduates generated seven important events that were likely to occur in the life of a newborn. Pleasantness and whether events were expected to occur between the ages of 15 and 30 years predicted how frequently events were recorded. Life scripts provide an alternative explanation of the reminiscence bump. Emphasis is on culture, not individuals.

Adult↗
PubMed2002

The pigeon's discrimination of visual entropy: a logarithmic function.

We taught 8 pigeons to discriminate 16-icon arrays that differed in their visual variability or "entropy" to see whether the relationship between entropy and discriminative behavior is linear (in which equivalent differences in entropy should produce equivalent changes in behavior) or logarithmic (in which higher entropy values should be less discriminable from one another than lower entropy values). Pigeons received a go/no-go task in which the lower entropy arrays were reinforced for one group and the higher entropy arrays were reinforced for a second group. The superior discrimination of the second group was predicted by a theoretical analysis in which excitatory and inhibitory stimulus generalization gradients fall along a logarithmic, but not a linear scale. Reanalysis of previously published data also yielded results consistent with a logarithmic relationship between entropy and discriminative behavior.

Animals↗
PubMed2001

Visual search: efficiency continuum or distinct processes?

Whether visual search involves two distinct processes--traditionally referred to as serial and parallel--or a single process operating on a continuum of efficiency or speed, is an issue with a long history in the study of attention. On the basis of the unimodality of search slope distributions in a very large data set, Wolfe (1998) argued for a continuum model. Reanalysis of this data set using statistical procedures more appropriate for adjudicating between continuous and discontinuous models supports the existence of two distinct processes.

Algorithms↗