Biomedical subjects

Peter A White

Publications and source records attributed to Peter A White.

At least 19 recordsLinked to original sources

PubMed2006

The role of activity in visual impressions of causality.

Phenomenal causality is an illusion built on an incomplete perception. It is an illusion because we can have visual impressions of causality when no interaction between objects is actually taking place. It is an illusion built on an incomplete perception because causality as we understand it neglects some factors involved in objective descriptions of interactions between objects in terms of the laws of mechanics. So, why don't we perceive object interactions in accordance with the laws of mechanics? I first consider what kinds of things can and cannot be causes perceptually, arguing that active objects can be causes and non-moving objects cannot be. Then, I argue that causal understanding originates with what we have the most direct experience of, our own actions on objects, and extends out from this point of origin to other domains of causality by a form of schema matching the interpretation of stimulus input by matching to abstracted stored representations of experiences. Schema matching raises the possibility of many more kinds of phenomenal causality than have hitherto been considered, and I conclude by suggesting some possibilities.

Cognition↗

PubMed2006

Detection of human sapovirus by real-time reverse transcription-polymerase chain reaction.

Sapovirus (SaV) is an agent of gastroenteritis for humans and swine, and is divided into five distinct genogroups (GI-GV) based on its capsid gene sequences. Typical methods of SaV detection include electron microscopy (EM), enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR). A novel TaqMan-based real-time RT-PCR assay was developed that is sensitive and has the ability to detect the broad range of genetically diverse human SaV strains. A nucleotide alignment of 10 full-length SaV genome sequences was subjected to similarity plot analysis, which indicated that the most conserved site was the polymerase-capsid junction in open reading frame 1 (ORF1). Based on multiple alignments of the 27 available sequences encoding this junction, we designed sets of primers and TaqMan MGB probes that detect human SaV GI, GII, GIV, and GV sequences in a single tube. The reactivity was confirmed with SaV GI, GII, GIV, and GV control plasmids, and the efficiency ranged from 2.5 x 10(7) to 2.5 x 10(1) copies per tube. Analysis using clinical stool specimens revealed that the present system was capable of detecting SaV GI, GII, GIV, and GV sequences, and no cross-reactivity was observed against other enteric viruses, including norovirus (NoV), rotavirus, astrovirus, and adenovirus. This is the first real-time RT-PCR system that could detect all genogroups of human sapoviruses.

Australia↗

PubMed2006

The causal asymmetry.

It is hypothesized that there is a pervasive and fundamental bias in humans' understanding of physical causation: Once the roles of cause and effect are assigned to objects in interactions, people tend to overestimate the strength and importance of the causal object and underestimate that of the effect object in bringing about the outcome. This bias is termed the causal asymmetry. Evidence for this bias is reviewed in several domains, including visual impressions of causal relations, reasoning about Newton's third law in naive physics problems, concepts underlying linguistic expressions of causality, and research in causal judgment from contingency information. Although there might be an equivalent to the causal asymmetry in the domain of social causality, there are too many uncertainties in the evidence for conclusions to be drawn.

Group Processes↗

PubMed2006

High-affinity aptamers to subtype 3a hepatitis C virus polymerase display genotypic specificity.

Research into antiviral agents directed at hepatitis C virus (HCV) proteins is commonly based and tested on a single genotype, namely, genotype 1. This is despite the high level of variability of the RNA virus and the frequency of infection with genotypes other than genotype 1. The systematic evolution of ligands by exponential enrichment (SELEX) is a novel in vitro approach used in this study that allows rapid screening of vast nucleic acid libraries to isolate sequences (termed aptamers) that bind to target proteins with high affinity. The SELEX approach was used in the present study to isolate DNA aptamers to the RNA-dependent RNA polymerase (RdRp) (nonstructural protein 5B [NS5B]) of HCV subtype 3a, with the aim of inhibiting polymerase activity. Ten rounds of selection were performed using a Biacore 2000 as the partitioning system. Two aptamers, r10/43 and r10/47, were chosen for further studies on the basis of their abilities to bind the HCV RdRp and inhibit polymerase activity. The affinities (equilibrium dissociation constants) of these aptamers for the HCV subtype 3a polymerase were estimated to be 1.3 +/- 0.3 nM (r10/43) and 23.5 +/- 6.7 nM (r10/47). The inhibition constants of r10/43 and r10/47 were estimated to be 1.4 +/- 2.4 nM and 6.0 +/- 2.3 nM, respectively. Inhibition of HCV 3a polymerase was specific for r10/47, while r10/43 also demonstrated some inhibitory effect on norovirus and phi6 polymerase activity. Neither r10/43 nor r10/47 was able to inhibit the RdRp activity of HCV genotype 1a and 1b polymerases. This study is the first description of an inhibitor specific to the HCV subtype 3a polymerase.

Aptamers, Nucleotide↗

PubMed2006

Emergence of a new norovirus genotype II.4 variant associated with global outbreaks of gastroenteritis.

Norovirus (NoV) is highly infectious and is the major cause of outbreak gastroenteritis in adults, with pandemic spread of the virus being reported in 1995 and 2002. The NoV genome is genetically diverse, which has hampered development of sensitive molecular biology-based methods. In this study we report on a nested reverse transcriptase PCR (nRT-PCR) that was designed to amplify the highly conserved 3' end of the polymerase region and the 5' end of the capsid gene of NoV genogroup II (GII). The nRT-PCR was validated with strains isolated from sporadic and outbreak cases between 1997 and 2004 in New South Wales, Australia. Phylogenetic analysis identified six genotypes circulating in New South Wales, GII.1, GII.3, GII.4, GII.6, GII.7, and GII.10, with GII.4 being the predominant genotype. In 2004, there was a marked increase in NoV GII activity in Australia, with a novel GII.4 variant being identified as the etiological agent in 18 outbreaks investigated. This novel GII.4 variant, termed Hunter virus, differed by more than 5% at the amino acid level across the capsid from any other NoV strain in the GenBank and EMBL databases. The Hunter virus was subsequently identified as the etiological agent in large epidemics of gastroenteritis in The Netherlands, Japan, and Taiwan in 2004 and 2005.

3' Untranslated Regions↗

PubMed2006

Genetic diversity of Sapovirus in children, Australia.

Sapovirus was detected in 7 of 95 stool specimens from children with gastroenteritis of unknown etiology in Sydney, Australia, from August 2001 to August 2002 and from February 2004 to August 2004, by using reverse transcription-polymerase chain reaction. Sequence analysis of the N-terminal capsid region showed all human sapovirus genogroups.

Australia↗

PubMed2005

Human enterovirus isolates from an outbreak typed using heteroduplex mobility analysis.

Genotyping and serotyping of enteroviruses is important for epidemiological, prognostic, and therapeutic reasons. In this study clinical isolates of enterovirus 71 during an outbreak of childhood meningoencephalitis in Sydney, Australia were identified using heteroduplex mobility analysis (HMA) of products from RT-PCR amplification of the 5' untranslated region. Five enterovirus 71 isolates shared identical heteroduplex patterns and nucleotide sequences in the 5' untranslated region. A sixth isolate exhibited minor differences in heteroduplex pattern and sequencing confirmed the isolate varied by 1% at the nucleotide level. The use of multiple reference strains and the analysis of heteroduplex patterns increased the confidence of isolate identification, and allowed identification of strain variation which could be subsequently further analyzed using sequencing. HMA can be used to accurately distinguish identical and variant isolates derived from sporadic cases and clustered infections with enteroviruses, including those causing serious infections.

5' Untranslated Regions↗

PubMed2005

The power PC theory and causal powers: comment on Cheng (1997) and Novick and Cheng (2004).

It has been claimed that the power PC theory reconciles regularity and power theories of causal judgment by showing how contingency information is used for inferences about unobservable causal powers. Under the causal powers theory causal relations are understood as generative relations in which a causal power of one thing acts on a liability of another thing under some releasing condition. These 3 causal roles are implicit or explicit in all causal interpretations. The power PC theory therefore fails to reconcile power theories and regularity theories because it has a fundamentally different definition of power and does not accommodate the tripartite causal role distinction. Implications of this distinction are drawn out.

Cognition↗

PubMed2005

Visual impressions of interactions between objects when the causal object does not move.

Stimuli were presented that consisted of a stationary row of black-bordered white rectangles. As observers watched, each rectangle in turn from left to right changed from white to black. The final rectangle did not change colour but moved off from left to right. The sequential colour change suggested motion from left to right, and observers reliably reported a visual impression that this illusory motion kicked or bumped the last rectangle, thereby making it move. The impression was stronger when the sequential colour change was faster, but was not significantly affected by the number of the rectangles in the row (ranging from 2 to 8). These results support the conclusion that neither contact nor motion of a causal object is necessary for a visual impression of causality to occur.

Causality↗

PubMed2005

Judgement of two causal candidates from contingency information: II. Effects of information about one cause on judgements of the other cause.

When judgements are being made about two causes there are eight possible kinds of contingency information: occurrences and nonoccurrences of the outcome when both causes are present, when Cause 1 alone is present, when Cause 2 alone is present, and when neither cause is present. It is proposed that contingency information is used to some extent to judge proportionate strength, which is the proportion of occurrences of the outcome that each cause can account for. This leads to a prediction that judgements of one cause will be influenced by information about occurrences, but not nonoccurrences, of the outcome when only the other cause is present. In six experiments consistent support was found for this prediction when the cause being judged had a positive relation with the outcome, but no consistent tendency was found when the cause being judged had a negative relation with the outcome. The effects found for causes with positive contingency cannot be explained by the Rescorla-Wagner model of causal judgement nor by the hypothesis that causal judgements are based on conditional contingencies.

Cues↗

PubMed2005

Cue interaction effects in causal judgement: an interpretation in terms of the evidential evaluation model.

In judging the extent to which a cue causes an outcome, judgement can be affected by information about other cues that are correlated with the one being judged. These cue interaction effects have usually been interpreted in terms of associative learning processes. I propose that a different model of causal judgement, the evidential evaluation model, offers a viable alternative interpretation of cue interaction phenomena. Under the evidential evaluation model, instances of contingency information are interpreted as evidence, which is confirmatory, disconfirmatory, or irrelevant for the cue being judged. When two cues co-occur in a set of instances the evidential value of the instances for one of them is determined by three factors: the proportion of confirming instances in the set; disambiguation value, which concerns the relation between the set of information and prior beliefs about the co-occurring cue; and confirmation value, which concerns the relation between the set of information and prior beliefs about the cue being judged. Any previous judgement of the cue is then modified in the light of these. It is shown that this model can account for all the cue interaction phenomena that have been investigated in studies of human causal judgement. The model also generates novel predictions, and the results of three experiments give support to these predictions. It is also shown that several other current models of causal judgement fail to predict a key result from Experiment 3.

Analysis of Variance↗

PubMed2005

The aadB gene cassette is associated with blaSHV genes in Klebsiella species producing extended-spectrum beta-lactamases.

Integrons were detected in 37 (72.5%) of 51 Klebsiella spp. producing extended-spectrum beta-lactamases by PCR with primers that targeted integrase genes and cassette regions. PCR and amplicon sequencing of the cassette regions revealed aadB and aadA2 gene cassettes that confer resistance to a range of aminoglycosides. aadB was associated with a class 1 integron on a 28-kb plasmid, pES1, that also contained bla(SHV-12) and IS26.

Aminoglycosides↗

PubMed2005

In vitro assessment of the further potential for development of fluoroquinolone resistance in Neisseria meningitidis.

We examined the potential for the development of fluoroquinolone resistance in Neisseria meningitidis by cultivating two clinical isolates of meningococci in the presence of concentrations of ciprofloxacin at and about the predetermined MIC. The quinolone resistance determining regions (QRDRs) of gyrA and parC of 50 stable quinolone-resistant mutants derived in vitro were sequenced and compared with QRDR alterations reported in clinical isolates of quinolone-resistant meningococci and gonococci. MICs to ciprofloxacin and trovafloxacin were determined and sequence changes were correlated with quinolone MICs. Ciprofloxacin and trovafloxacin MICs of the in vitro-derived quinolone-resistant mutants ranged up to 16 mg/liter. Single GyrA alterations were the first change detected and were accompanied by raised MICs, followed by double GyrA changes and still higher MICs. MICs increased further as single ParC substitutions appeared and these were always in the presence of a single or double GyrA change. GyrA changes occurred at positions 91 and 95 with substitutions of Asp-95-->Asn and Thr-91-->Ala and Ile. Changes in the parC QRDR occurred at positions 85, 86, and 91 with four substitutions, Gly-85-->Asp, Asp-86-->Asn, Glu-91-->Gly, and Glu-91-->Lys, detected. The nature of the individual QRDR substitution appeared to influence the level of quinolone resistance expressed, and this varied with the quinolone agent examined. Close similarities occurred between the sequence and nature of QRDR changes in clinical and in vitro-generated quinolone-resistant mutants and with those previously reported for clinical and in vitro-generated quinolone-resistant gonococci. This suggests that quinolone resistance in meningococci may arise in the same manner and reach similar levels in vivo to those seen in quinolone-resistant Neisseria gonorrhoeae.

Amino Acid Substitution↗

PubMed2005

Norovirus recombination in ORF1/ORF2 overlap.

Norovirus (NoV) genogroups I and II (GI and GII) are now recognized as the predominant worldwide cause of outbreaks of acute gastroenteritis in humans. Three recombinant NoV GII isolates were identified and characterized, 2 of which are unrelated to any previously published recombinant NoV. Using data from the current study, published sequences, database searches, and molecular techniques, we identified 23 recombinant NoV GII and 1 recombinant NoV GI isolates. Analysis of the genetic relationships among the recombinant NoV GII isolates identified 9 independent recombinant sequences; the other 14 strains were close relatives. Two of the 9 independent recombinant NoV were closely related to other recombinants only in the polymerase region, and in a similar fashion 1 recombinant NoV was closely related to another only in the capsid region. Breakpoint analysis of recombinant NoV showed that recombination occurred in the open reading frame (ORF)1/ORF2 overlap. We provide evidence to support the theory of the role of subgenomic RNA promoters as recombination hotspots and describe a simple mechanism of how recombination might occur in NoV.

Caliciviridae Infections↗

PubMed2004

Clearance of hepatitis C virus after newly acquired infection in injection drug users.

A retrospective cohort of injection drug users with newly acquired hepatitis C virus (HCV) infection was established to examine viral clearance. Newly acquired HCV infection was defined by anti-HCV antibody seroconversion within a 2-year interval. Stored serum samples were tested for HCV RNA, with viral clearance defined as >/=2 consecutive negative HCV RNA test results after infection. Ninety-nine cases of HCV infection were identified; 57 had >/=2 HCV RNA test results after infection. Viral clearance occurred in 24 (42%) cases, with Kaplan-Meier estimated probabilities of 23%, 38%, and 40% at 6, 12, and 24 months, respectively.

Adolescent↗

PubMed2004

Prevalence of production of virus-specific interferon-gamma among seronegative hepatitis C-resistant subjects reporting injection drug use.

This report describes subjects who were highly likely to have been repeatedly exposed to hepatitis C virus (HCV) through injection drug use and who remained negative for anti-HCV antibody. Production of virus-specific interferon- gamma by peripheral blood mononuclear cells was seen in the majority of subjects (72%) and was associated with higher-risk behavior. For 92% of the subjects, results of recombinant immunoblot assays demonstrated faint bands against nonstructural proteins. The immune responses described are likely to have been primed and maintained by episodes of subclinical infection without classic seroconversion and may indicate a hepatitis C-resistant phenotype. Vaccine strategies to mimic this response may provide protection against persistent HCV infection.

Adolescent↗

PubMed2004

Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort.

Understanding the earliest virological and immunological events in acute hepatitis C virus (HCV) infection may provide insight into the determinants of protective immunity. Four cases of HCV viremia with subsequent viral clearance, but without biochemical hepatitis or anti-HCV seroconversion, are reported from a prospective cohort study of prison inmates. Two of the subjects who developed sustained viremia were assessed for production of interferon (IFN)- gamma, by use of the enzyme-linked immunospot (ELISPOT) method and by assessment of HCV cytotoxic T lymphocyte (CTL) activity, CD4 lymphocyte proliferative responses, HCV load, and genotype. After 2-6 months of viremia, all 4 subjects cleared serum HCV RNA. Specific cellular responses were detected in both of the subjects who were assessed, and production of IFN- gamma was demonstrated in one subject. All subjects had weak, but consistent, serological reactivity against HCV nonstructural proteins on immunoblot testing, despite repeatedly nonreactive HCV ELISA tests. These cases highlight the potential for cellular immune responses against HCV to facilitate viral clearance, responses that may model those required for effective HCV vaccination.

Adult↗

PubMed2004

Causal judgment from contingency information: a systematic test of the pCI rule.

Contingency information is information about the occurrence or nonoccurrence of an effect when a possible cause is present or absent. Under the evidential evaluation model, instances of contingency information are transformed into evidence and causal judgment is based on the proportion of relevant instances evaluated as confirmatory for the candidate cause. In this article, two experiments are reported that were designed to test systematic manipulations of the proportion of confirming instances in relation to other variables: the proportion of instances on which the candidate cause is present, the proportion of instances in which the effect occurs when the cause is present, and the objective contingency. Results showed that both unweighted and weighted versions of the proportion-of-confirmatory-instances rule successfully predicted the main features of the results, with the weighted version proving more successful. Other models, including the power PC theory, failed to predict the results.

Decision Making↗