Sequential Sampling Models in Cognitive Neuroscience: Advantages, Applications, and Extensions.

Sequential sampling models assume that people make speeded decisions by gradually accumulating noisy information until a threshold of evidence is reached. In cognitive science, one such model--the diffusion decision model--is now regularly used to decompose task performance into underlying processes such as the quality of information processing, response caution, and a priori bias. In the cognitive neurosciences, the diffusion decision model has recently been adopted as a quantitative tool to study the neural basis of decision making under time pressure. We present a selective overview of several recent applications and extensions of the diffusion decision model in the cognitive neurosciences.

Identification of Legionella spp. by 19 European reference laboratories: results of the European Working Group for Legionella Infections External Quality Assessment Scheme using DNA sequencing of the macrophage infectivity potentiator gene and dedicated online tools.

Identification of Legionella spp. can be achieved by DNA sequencing of the macrophage infectivity potentiator (mip) gene. The External Quality Assurance (EQA) scheme described in this report is the first to assess the proficiency of laboratories using this methodology. The results obtained from two EQA distributions sent to European reference laboratories involved in Legionella outbreak control and environmental monitoring are presented. Each distribution contained a panel of ten coded Legionella strains. All strains were from clinical and environmental sources and were considered to be wild-type strains. Participants used dedicated online tools to compare sequence text files against a database of known Legionella spp. The majority of centres (seven of ten, and 11 of 12) correctly identified all strains tested, in the first and second distributions, respectively. Typically, sequence similarity values of 98-100% were obtained when the test strains were compared with sequences contained in the database. In all but one case, lower values indicated a poor quality sequence. The exception was associated with the identification of a putative new species in the first panel. Genotypic identification of Legionella can be achieved by the use of standard protocols, dedicated identification libraries, and online tools. EQA schemes provide an independent measure of performance, and it is recommended that laboratories performing these techniques participate in such schemes, thereby allowing optimisation of and improvements in their performance.

Internationally distributed frozen oyster meat causing multiple outbreaks of norovirus infection in Australia.

BACKGROUND: Between November 2003 and January 2004, outbreaks of norovirus in 3 Australian jurisdictions involving 83 cases of illness were associated with imported oyster meat. METHODS: Cohort studies were conducted in 2 jurisdictions to identify relative risks of illness for the consumption of oysters. A case series was conducted in the third jurisdiction. RESULTS: The cohort studies conducted in the first 2 jurisdictions identified relative risks of illness of 17 (95% confidence interval, 5-51) and 35 (95% confidence interval, 5-243), respectively, for the consumption of oysters. Multiple strains of norovirus were detected in fecal specimens from 8 of 14 patients and in 1 of the 3 batches of implicated oyster meat using seminested reverse-transcriptase polymerase chain reaction methods. Traceback investigations revealed that all oyster meat was harvested from the same estuary system in Japan within the same month. CONCLUSIONS: These outbreaks demonstrate the potential of foodborne disease to spread internationally and the need for national and international collaboration to investigate such outbreaks. Foodborne illness related to norovirus is underestimated because of underreporting of human cases and challenges in laboratory detection of viruses in foods, both of which can delay public health action.

Expression and regulation of the Na+-K+-2Cl- cotransporter NKCC1 in the normal and CFTR-deficient murine colon.

Defective regulation and/or reduced expression of the Na+-K+-2Cl- cotransporter NKCC1 may contribute to the severe secretory defect that is observed in cystic fibrosis, but data concerning the expression and function of NKCC1 in cystic fibrosis transmembrane conductance regulator (CFTR)-deficient cells are equivocal. We therefore investigated NKCC1 mRNA expression, Na+-K+-2Cl- cotransport activity and regulation by cAMP in crypts isolated from the proximal colon of CFTR-containing (CFTR (+/+)) and CFTR-deficient (CFTR (-/-)) mice. mRNA expression levels were determined by semiquantitative PCR, transport rates were measured fluorometrically in 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetomethylester (BCECF)-loaded crypts, cytoplasmic volume changes were assessed by confocal microscopy, and [Cl-]i changes were examined by N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) quenching. NKCC1 mRNA expression levels were not significantly reduced in CFTR (-/-) crypts compared to controls. Azosemide-sensitive NH4+ influx (used as a measure of Na+-K+-2Cl- cotransport) was 2.23 +/- 0.72 vs. 1.56 +/- 0.16 mM min-1, and increased by 63.6 % in (+/+) and 87.3 % in (-/-) crypts upon stimulation for 5 min with forskolin. After 20 min of stimulation with forskolin, the Na+-K+-2Cl- cotransport rates in (-/-) and (+/+) crypts were identical. Crypt cross-sectional area and [Cl-]i decreased only in (+/+) crypts upon stimulation. In conclusion, normal NKCC1 expression levels, somewhat reduced Na+-K+-2Cl- cotransport rates, but preserved activation by cAMP were found in colonic crypts from CFTR (-/-) mice, ruling out a severe dysfunction of the Na+-K+-2Cl- cotransporter in the CF intestine. Furthermore, these studies establish the existence of a direct, cell-volume- and [Cl-]i-independent activation of colonic NKCC1 by an increase in intracellular cAMP.

cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3- cotransporter subtype pNBC1.

Basolateral Na(+)-HCO(3)(-) cotransport is essential for intestinal anion secretion, and indirect evidence suggests that it may be stimulated by a rise of intracellular cAMP. We therefore investigated the expression, activity, and regulation by cAMP of the Na(+)-HCO(3)(-) cotransporter isoforms NBC1 and NBCn1 in isolated murine colonic crypts. Na(+)-HCO(3)(-) transport rates were measured fluorometrically in BCECF-loaded crypts, and mRNA expression levels and localization were determined by semiquantitative PCR and in situ hybridization. Acid-activated Na(+)-HCO(3)(-) cotransport rates were 5.07 +/- 0.7 mM/min and increased by 62% after forskolin stimulation. NBC1 mRNA was more abundant in colonic crypts than in surface cells, and crypts expressed far more NBC1 than NBCn1. To investigate whether the cAMP-induced Na(+)-HCO(3)(-) cotransport activation was secondary to secretion-associated changes in HCO(3)(-) or cell volume, we measured potential forskolin-induced changes in intracellular pH and assessed Na(+)-HCO(3)(-) transport activity in CFTR -/- crypts (in which no forskolin-induced cell shrinkage occurs). We found 30% reduced Na(+)-HCO(3)(-) transport rates in CFTR -/- compared with CFTR +/+ crypts but similar Na(+)-HCO(3)(-) cotransport activation by forskolin. These studies establish the existence of an intracellular HCO(3)(-) concentration- and cell volume-independent activation of colonic NBC by an increase in intracellular cAMP.

Molecular diversity of Campylobacter coli and C. jejuni isolated from pigs at slaughter by flaA-RFLP analysis and ribotyping.

A population of porcine isolates of Camplobacter jejuni (n = 11) and C. coli (n = 17) were examined for genotypic relatedness employing ribotyping, as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the flagellin (fla)A gene locus. PCR was employed to amplify a 533 bp fragment from the flaA gene, including the previously described short variable region (SVR), employing the novel primers, A2 and Al and successfully generated this amplicon for all wild-type strains examined (n = 28) of both C. jejuni and C. coli, as well as with both type strains, i.e. C. jejuni NCTC 11351 and C. coli NCTC 11366. Individual genotypes were assigned to each isolate typed employing the four typing methods (flaA-RFLP(Hae) III, flaA-RFLP(Pst) I ribotyping(Hae) III and ribotyping(Pst) I) and were assigned an arbitrary genotype code in ascending alphabetical order in comparison with a database of established genotypes for each of the methods employed. This study showed that several flaA-RFLP and ribopatterns existed within C. jejuni and C. coli, and demonstrated a heterogeneous diversity of strains occurring in the pigs examined. Ribotyping of strains with 16S and 23S rRNA with Pst I and Hae III digested chromosomal DNA allowed subdivision of strains into nine and eight groups, respectively. RFLP analyses with Pst I and Hae III digests probed with the flaA gene probe allowed subdivision of strains into eight and eleven subtypes, respectively. Employment of RFLP with the flaA nucleic acid probe and Hae III digests produced the greatest amount of variation of any genotyping scheme employed. Although there was a high degree of variability demonstrated by both typing methods, most isolates ( > 60%) clustered into four main genotypes, i.e. genotypes A-D. FlaA-PCR-RFLP typing demonstrated that the majority of isolates, 67.9 and 60.7%, were included in these four main genotypes for Pst I and Hae III restriction digests, respectively, although there was a high prevalence (7/11; 63.6%) of fla(Hae) III genotype A occurring within the C. jejuni isolates. Likewise, ribotyping studies demonstrated that most isolates were clustered into these four main genotypes, accounting for 81.5 and 60.7% of isolates for Pst I and Hae III restriction digests, respectively. This may indicate that the clonal population of campylobacters within this pig population is largely composed of persistent and dominant types, with a smaller number of hypervariable subtypes. Such data may useful in determining epidemiological routes of transmission of campylobacters from animal to animal, as well as helping to identify virulence determinants in persistent subtype populations.

A novel approach to pathogen reduction in biosolids: the enzymic hydrolyser.

Revision of the Sludge (Use in Agriculture) Regulations in the UK has resulted in the requirement of a final product standard in terms of E. coli per gram of dry solids. Conventional mesophilic digestion including 14-day secondary storage should normally provide adequate treatment to meet the Treated Sludge Standard. Any process capable of greater pathogen reduction would ensure more process security and compliance comfort. Such a process would be a welcome alternative to extra secondary storage where an existing works does not have sufficient capacity, particularly if the differences in costs between the options are small. Enzymic hydrolysis was found to be up to ten-fold more effective in E. coli reduction than conventional secondary digestion. A two-stage digestion process based on this technique has been developed by United Utilities and Montgomery Watson Harza (termed the enzymic hydrolyser, patent pending). Studies showed that the mean numbers of E. coli were significantly lower in the enzymic hydrolyser systems (P > 0.05; t = 13.19) compared to conventional digesters. Increased stability was a secondary benefit of the system (foam was eliminated or greatly reduced in the enzymic hydrolyser units). Another benefit of the system for retrofit to existing assets is the decreased tankage volumes required compared to secondary digestion to achieve more than twice the log kill of pathogens.

A multinomial model for short-term priming in word identification.

A simple multinomial model for short-term priming in perceptual word identification is presented. In the experiments to which the model is applied, prime words are presented just prior to a flashed target word, and subjects must decide which of 2 alternative words matches the target. The model assumes that on some proportion of trials, confusion among the words leads to the decision being based on 1 of the prime words instead of the target. In addition, it is assumed that subjects sometimes discount a prime that matches 1 of the test alternatives and so choose the alternative that does not match. With these assumptions, the model fits the data from 5 experiments (including 4 used to develop the model known as ROUSE [responding optimally with unknown sources of evidence]; D. E. Huber, R. Shiffrin, K. Lyle, & K. Ruys, 2001). The multinomial model fits the data about as well as the ROUSE model and so should lead to further development and critical testing of both models.

Counter model for word identification: reply to Bowers (1999).

The counter model (R. Ratcliff & G. McKoon, 1997) was designed to explain the normal processes of word identification and how they are influenced by a prior encounter with a word. The model accounts for the findings of word identification experiments in which words are flashed briefly. A crucial finding is that prior encounters with words typically lead to biases such that a previously encountered word is more likely to be given as a response. However, for low-frequency words, a prior encounter can improve overall performance (J. S. Bowers, 1999; E. M. Wagenmakers, R. Zeelenberg, & J. G. W. Raaijmakers, 2000). The authors show how the model can explain this result. Also, J. S. Bowers (1999) has claimed that some earlier data concerning dissimilar alternatives in forced-choice experiments that support the counter model are spurious, but the authors show that his claims are incorrect. In sum, the authors argue for a theoretical approach that offers a detailed description of the cognitive processes of word identification and explains performance across tasks, measures, and independent variables.

Legionella drozanskii sp. nov., Legionella rowbothamii sp. nov. and Legionella fallonii sp. nov.: three unusual new Legionella species.

Seven strains of Legionella-like amoebal pathogens (LLAPs) were characterized on the basis of their cultural and staining characteristics, biochemical reactions, serology, cellular fatty acids (CFAs), isoprenoid quinone composition, total DNA relatedness, analysis of 16S rRNA and macrophage infectivity potentiator (mip) gene sequence analyses. All seven strains exhibited limited growth on buffered charcoal yeast extract alpha (BCYE) agar, required cysteine for growth and contained branched-chain CFAs and quinones typical of Legionella species. The bacilli were Gram-negative and catalase-positive. There were varying degrees of serological cross-reactions between these LLAP strains and other previously described Legionella species. Results from the various tests revealed that four LLAP strains represent three unusual new species of Legionella: Legionella drozanskii sp. nov., type strain LLAP-1T; Legionella rowbothamii sp. nov., type strain LLAP-6T; and Legionella fallonii sp. nov., type strain LLAP-10T. Three other LLAP strains, designated LLAP-7FL, LLAP-7NF and LLAP-9, were shown to be members of the species Legionella lytica. The deductions made from the phenetic characteristics of these bacteria were consistent with the phylogenetic relationships inferred from 16S rRNA and mip gene sequence analyses. This study is the first to speciate LLAP strains on the basis of data including quantitative DNA hybridization.

The effects of aging on reaction time in a signal detection task.

The effects of aging on response time are examined in 2 simple signal detection tasks with young and older subjects (age 60 years and older). Older subjects were generally slower than young subjects, and standard Brinley plot analyses of response times showed typical results: slopes greater than 1 and (mostly) negative intercepts. R. Ratcliff, D. Spieler, and G. McKoon (2000) showed that the slopes of Brinley plots measure the relative standard deviations of the distributions of response times for older versus young subjects. Applying R. Ratcliff's (1978) diffusion model to fit the response times, their distributions, and response accuracy, it was found that the larger spread in older subjects' response times and their slowness relative to young subjects comes from a 50-ms slowing of the nondecision components of response time and more from conservative settings of response criteria.

A comparison of four methods for simulating the diffusion process.

Four methods for the simulation of the Wiener process with constant drift and variance are described. These four methods are (1) approximating the diffusion process by a random walk with very small time steps; (2) drawing directly from the joint density of responses and reaction time by means of a (possibly) repeated application of a rejection algorithm; (3) using a discrete approximation to the stochastic differential equation describing the diffusion process; and (4) a probability integral transform method approximating the inverse of the cumulative distribution function of the diffusion process. The four methods for simulating response probabilities and response times are compared on two criteria: simulation speed and accuracy of the simulation. It is concluded that the rejection-based and probability integral transform method perform best on both criteria, and that the stochastic differential approximation is worst. An important drawback of the rejection method is that it is applicable only to the Wiener process, whereas the probability integral transform method is more general.

Explicitly modeling the effects of aging on response time.

Research into the effects of aging on response time has focused on Brinley plots. Brinley plots are constructed by plotting mean response times for older subjects against those for young subjects for a set of experimental conditions. The typical result is a straight line with a slope greater than 1 and a negative intercept. This linear function has been interpreted as showing that aging leads to a general slowing of cognitive processes. In this article, we show that the slope of the Brinley plot is actually a measure of the relative standard deviations of older versus young subjects' response times; it is not a measure of general slowing. We examine current models of the effects of aging on mean response time and show how they might be reinterpreted. We also show how a more comprehensive model, Ratcliff's diffusion model (1978), can account for Brinley plot regularities and, at the same time, provide an account of accuracy rates, the shapes of response time distributions, and the relative speeds of error and correct response times, aspects of the data about which models designed to account for Brinley plots are mute. We conclude by endorsing a research approach that applies explicit models to response time data in aging in order to use the parameters of the model to interpret the effects of aging.

A diffusion model account of masking in two-choice letter identification.

The diffusion model developed by R. Ratcliff (1978, 1981, 1985, 1988) for 2-choice decisions was applied to data from 2 letter identification experiments. In the experiments, stimulus letters were displayed and then masked, and the stimulus onset asynchrony between letter and mask was manipulated to vary accuracy from near chance to near ceiling. A standard reaction time procedure was used in one experiment and a deadline procedure in the other. Two hypotheses about the effect of masking on the information provided to the decision process were contrasted: (a) The output of perception to the decision process varies with time, so that the information used by the decision process rises and falls, reflecting the stimulus onset and mask onset. (b) The output of perception to the decision is constant over time, reflecting information integrated over the time between the stimulus and mask onsets. The data were well fit by the diffusion model only with the assumption of constant information over time.

Sodium channel blockers and uridine triphosphate: effects on nasal potential difference in cystic fibrosis mice.

Sodium channel inhibitors block the enhanced Na+ reabsorption in cystic fibrosis (CF). Extracellular nucleotides facilitate Cl- secretion via Ca2+ gated Cl- channels. A combination of these effects may produce less viscid secretions in CF which are easier to expectorate. This study examined the effects of combining sodium channel blockers with uridine triphosphate (UTP) on nasal membrane potential difference (PD) in CF insertional null mutant mice (cftr(tm1HGU)), deltaF508 homozygous mice (cftr(tm1Cam)) and matched control animals. Median basal PD in the insertional CF mice and deltaF508 CF mice were -28 and -34 mV respectively. These values were significantly different to the control animals (-20 mV). Amiloride and loperamide reduced the PD in cftr(tm1HGU) CF mice (deltaPD 13 mV & 15 mV respectively) suggesting Na+ blockade. The subsequent addition of UTP in a chloride-free vehicle increased the PD (deltaPD -8- -12.5 mV). DeltaF508 mice showed significantly greater responses compared with CF insertional null mutant mice (p<0.05). The action of UTP was brief and not prolonged by the addition alpha-beta-methylene-adenosine 5' diphosphate. Suramin, a competitive antagonist of P2 purinoceptors blocked the action of UTP. In conclusion, this study demonstrated dose dependant nasal membrane potential changes in differences mice with uridine triphosphate in the presence of sodium channel blockers suggestive of chloride secretion. More stable analogues of uridine triphosphate in combination with long acting sodium channel blockers such as loperamide may have therapeutic potential in cystic fibrosis.

Modeling the effects of repetition and word frequency in perceptual identification.

The counter model for word identification (Ratcliff & McKoon, 1997) has been challenged by recent empirical findings that performance on low-frequency words improves as the result of repetition of the words. We show that the model can accommodate this learning effect, and that it can do so without jeopardizing its explanations of the effects on word identification of a large number of other variables.

A neural network model of implicit memory for object recognition.

People name well-known objects shown in pictures more quickly if they have studied them previously. The most common interpretation of this priming effect is that processing is facilitated by an implicit memory trace in a perceptual representation system. We show that object priming can be explained instead as a bias in information processing, without recourse to an implicit memory system. Assumptions about psychological decision-making processes and bias were added to a neural network model for object identification, and the model accounted for performance both qualitatively and quantitatively in four object identification experiments.

Connectionist and diffusion models of reaction time.

Two connectionist frameworks, GRAIN (J. L. McClelland, 1993) and brain-state-in-a-box (J. A. Anderson, 1991), and R. Ratcliff's (1978) diffusion model were evaluated using data from a signal detection task. Dependent variables included response probabilities, reaction times for correct and error responses, and shapes of reaction-time distributions. The diffusion model accounted for all aspects of the data, including error reaction times that had previously been a problem for all response-time models. The connectionist models accounted for many aspects of the data adequately, but each failed to a greater or lesser degree in important ways except for one model that was similar to the diffusion model. The findings advance the development of the diffusion model and show that the long tradition of reaction-time research and theory is a fertile domain for development and testing of connectionist assumptions about how decisions are generated over time.

Hepatitis C genotyping by direct sequencing of the product from the Roche AMPLICOR test: methodology and application to a South Australian population.

The Roche AMPLICOR RT-PCR amplifies a 244 nucleotide sequence within the 5' non coding region (5'NCR) of the viral genome and is a widely used commercial test for the qualitative determination of hepatitis C RNA from sera. This paper describes a routine procedure for the purification of the PCR product, and its use in automated DNA sequencing, for determining the genotype of hepatitis C virus (HCV) isolates. Direct sequencing of the purified product was possible for 86% of samples, whilst 14% required additional amplification using a nested PCR method in order to read the resulting electropherogram. This method of genotyping is considerably less expensive than currently available commercial kits, and is convenient for the increasing number of laboratories that have access to automated DNA sequencers. The highly conserved nature of the 5'NCR limited differentiation of types and subtypes to an extent comparable to commercial HCV typing methods. Using this method on available laboratory samples and on patients about to commence interferon therapy, we found a predominance of genotype 1 (59%) and 3a (31%). Analysis of data on the interferon patients showed the median length of time from first exposure to diagnosis to be significantly longer for patients with genotype 1 than genotype 3a.