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Biomedical subjects

E J Robinson

Publications and source records attributed to E J Robinson.

At least 19 recordsLinked to original sources

Can one written word mean many things? Prereaders' assumptions about the stability of written words' meanings.

Results of three experiments confirmed previous findings that in a moving word task, prereaders 3 to 5 years of age judge as if the meaning of a written word changes when it moves from a matching to a nonmatching toy (e.g., when the word "dog" moves from a dog to a boat). We explore under what circumstances children make such errors, we identify new conditions under which children were more likely correctly to treat written words' meanings as stable: when the word was placed alongside a nonmatching toy without having been alongside a matching toy previously, when two words were moved from a matching toy to a nonmatching toy, and when children were asked to change what the print said. Under these conditions, children more frequently assumed that physical forms had stable meanings as they do with other forms of external representation.

Child, Preschool↗

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

OBJECTIVES: To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. DESIGN: Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. SETTING: Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. PARTICIPANTS: Healthy adults with a wide range of educational backgrounds and ages. INVESTIGATIONS: Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. MAIN OUTCOME MEASURES: Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. RESULTS: Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. CONCLUSIONS: This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.

Adolescent↗

When can children handle referential opacity? Evidence for systematic variation in 5- and 6-year-old children's reasoning about beliefs and belief reports.

Five- and 6-year-olds (N=51) heard stories in which a character sorted items into two locations. Either the character had a false belief about one of the items (e.g., thought a tin contained biscuits, not Lego), or was only partially informed of an item's dual identity (e.g., did not know that a tie was a present). Children found it easier to reject a report of the character's belief that described the true state of affairs when the character had a false belief (e.g., Is Fred's uncle thinking "where shall I put this Lego?"), than to reject one in which an object known to the character was described using a term of which she was ignorant (e.g., Is Mum thinking "where shall I put this present?"). Similarly, children found it easier to predict the character's incorrect sorting of the target items for false belief (with food not toys) than for dual identity (in the wardrobe not with things to take on a visit). Correct reasoning about beliefs and reports of beliefs that misrepresent an object does not imply mastery of the fact that beliefs represent an object in a particular way.

Child↗

Five-year-olds' handling of reference and description in the domains of language and mental representation.

Children's concurrent success on false belief tasks and their handling of two labels for one object (e.g., bunny/rabbit) has been interpreted as demonstrating understanding about the essential features of representation. Three experiments reveal the limitations in 5-year-olds' understanding for both mental and linguistic representations. We report relatively poor performance on a task involving two labels for one object (e.g., dice/eraser) which required children to treat another's knowledge as representing only some of the feature of its real referent: Dice but not eraser. Five year olds who made errors also had difficulty handling the fact that a written word 'dice' referring to such a dice/eraser, can also be applied to a standard dice but not to a standard eraser. These children lacked metalinguistic awareness of words as entities that both refer and describe.

Analysis of Variance↗

Children's difficulties handling dual identity.

Thirty-nine 6-year-old children participated in a longitudinal study using tasks that required handling of dual identity. Pre- and posttest sessions employed tasks involving a protagonist who was partially informed about an object or person; for example, he knew an item as a ball but not as a present. Children who judged correctly that the protagonist did not know the ball was a present (thereby demonstrating some understanding of the consequences of limited information access), often judged incorrectly (1) that he knew that there was a present in the box, and (2) that he would search as if fully informed. Intervening sessions added contextual support and tried to clarify the experimenter's communicative intentions in a range of ways. Despite signs of general improvement, the distinctive pattern of errors persisted in every case. These findings go beyond previous studies of children's handling of limited information access, and are hard to accommodate within existing accounts of developing understanding of the mind.

Child↗

Children's ability to make tentative interpretations of ambiguous messages.

Consistent with prior research, 5- and 6-year-old children overestimated their knowledge of the intended referent of ambiguous messages. Yet they correctly revised their interpretations of ambiguous messages in light of contradicting information that followed immediately, while maintaining their initial interpretations of unambiguous messages (Experiment 1). Children of this age were able to integrate information over two successive ambiguous messages to identify the intended referent (Experiment 2). However, unlike 7- and 8-year-olds, they were no more likely to search for further information following ambiguous messages compared with unambiguous ones (Experiment 3). We conclude that although 5- and 6-year-olds' interpretations of ambiguous messages are not tentative at the outset, they can use source monitoring skills to treat them as tentative retrospectively, at least over short time spans.

Age Factors↗

Information presentation and decisions to enter clinical trials: a hypothetical trial of hormone replacement therapy.

We examined recruitment to an imaginary trial of hormone replacement therapy (HRT) following two different styles of information about HRT. We predicted that for treatments which, like HRT, are available outside a trial, people offered the facts as currently known would be less likely to remain unsure about the relative costs and benefits, and so less likely to agree to enter a randomised trial. In contrast, when the information provided reflected the current state of uncertainty which justified the trial, we predicted that people would be less likely to form a preference for one treatment arm over the other, and so more likely to agree to enter a trial. One hundred women aged 25-40 years were informed about HRT via a video and an information leaflet. For half the participants the information was framed in a way which emphasised the current state of uncertainty about the relative costs and benefits of HRT, and in that respect it reflected the justification for a trial. This version was considered to be similar in style to information commonly provided to potential trial participants. For half the participants the same information was framed in a way which offered explicit numerical detail about currently known facts, and in that respect it was considered to be similar in style to information commonly available to doctors prior to a trial. Women learned as much about HRT in the two conditions, but women given the explicit versions were more likely (i) to hold a stronger view about whether or not they would take HRT (ratings were not elicited from the first 30 participants in this condition. N = 20, p < 0.05 1 tailed) and (ii) to refuse entry to the trial (N = 50, p < 0.05 2 tailed). Those who, given the explicit version, agreed rather than refused to enter the trial, scored higher on believing that others control their health (p < 0.01 2 tailed).

Adult↗

High rates of infant macrosomia: a comparison of a Canadian native and a non-native population.

The Cree of James Bay have the highest ever reported mean birth weight and a high prevalence of infant macrosomia. This study was designed to examine independent risk factors for infant macrosomia among the Cree, to compare these to risk factors among non-Native Canadians and to determine if ethnic differences persist after adjusting for differences in the distribution of other risk factors. Macrosomia was defined as birth weight >90(th) percentile for gestational age of a reference population. Independent determinants of macrosomia were examined in 385 Cree and 5644 non-Native women. The potential effect of ethnicity (Cree vs. non-Native) was determined after statistically adjusting for age, parity, pregravid weight, height, net rate of weight gain, gestational diabetes mellitus (GDM) and smoking status. The prevalence of macrosomia among the Cree was 34.3% vs. 11.1% among non-Natives. Although GDM significantly increased the risk for macrosomia among the Cree (odds ratio: 4.46, 95% CI: 2.24-9.26), it was not a significant risk factor among non-Natives (odds ratio: 1.15, 95% CI: 0.79-1.65). The risk for infant macrosomia remained elevated among the Cree compared with non-Natives after adjusting for other risk factors (odds ratio: 3.64, 95% CI: 2.69-4.90). In conclusion, the Cree have a high prevalence of macrosomia despite controlling for important differences in pregravid weight and GDM. Some of this variation may be due to genetic differences in fetal growth. The differential impact of GDM on macrosomia in the two ethnic groups may be due to differences in treatment strategies for GDM.

Adult↗

Children's understanding that utterances emanate from minds: using speaker belief to aid interpretation.

Children interpreted an utterance made by a protagonist with a false belief, such as, 'I would like the car in the garage.' Calculating the speaker's belief in conjunction with the literal meaning of the utterance would lead to the correct interpretation that the intended referent is the car on the track, given that the car in the garage swapped places with the one on the track. In Experiments 1 and 2, many children aged around 4 and 5 years wrongly indicated the car in the garage. In contrast, many correctly indicated the car on the track when it was unnecessary to consider the speaker's belief because the utterance was, 'the car I put in the garage'. Six-year-olds found both kinds of utterance equally easy in Experiment 1, while 3-year-olds had equal difficulty with both. In Experiments 2 and 3, the speaker gave an ambiguous utterance and many children aged between 3 and 6 years successfully used information about the speaker's belief to identify which of several candidate referents was intended. We discuss the results in relation to characteristics of utterance comprehension and consider implications for developments in understanding the mind by children beyond 4 years.

Age Factors↗

Realist errors in children's responses to pictures and words as representations.

In three experiments we examined the judgments made by 3- to 4- year-old children about out-of-date physical representations which no longer matched their referents. The referent was a doll wearing a sticker, and the sticker was swapped for a different one after a picture had been drawn of the initial state of affairs (Experiments 1 and 2) or after the name of the doll and its original sticker had been written down (Experiment 3). We confirmed previous findings of realist errors in identity judgments for pictures and showed also that children tended to misidentify the name of a sticker in a written list to match a change to its referent. Thus, realist errors are not confined to representations which are iconically similar to their referents. Furthermore, children also judged incorrectly that the pictures and words had actually been changed, indicating that realist errors to external representations extend to operations performed on their referents as well as to their identities.

Child Language↗

Children's ability to infer utterance veracity from speaker informedness.

Children between the ages of 3 years 7 months and 6 years 5 months experienced a contradiction between what they knew or guessed to be inside a box and what they were told by an adult. The authors investigated whether children believed what they were told by asking them to make a final judgment about the box's content. Children tended to believe utterances from speakers who were better informed than they themselves were and to disbelieve those from less well-informed speakers, with no age-related differences. This behavior implies an understanding of the speaker's knowledge and suggests that children can learn from oral input while being appropriately skeptical of its truth. Children also gave explicit knowledge judgments on trials on which no utterances were given. Performance on knowledge trials was less accurate than, and unrelated to, performance on utterance trials. Research on children's developing explicit theory of mind needs to be broadened to include behavioral indexes of understanding the mind.

Adult↗

Interaction of body weight and ethnicity on risk of gestational diabetes mellitus.

BACKGROUND: The James Bay Cree of Canada have one of the highest recorded rates of gestational diabetes mellitus (GDM) among aboriginal people worldwide; the reasons for this elevated risk remain to be documented. OBJECTIVE: Our objective was to compare predictors and risk of GDM between the James Bay Cree and non-Native Canadians. DESIGN: Risk for GDM was compared between Cree and non-Native women by 1) adjusting statistically for differences in age, parity, pregravid weight, and smoking status (n = 402 Cree, 7718 non-Natives), and 2) matching Cree women with non-Native women for age and pregravid weight (n = 394 Cree, 788 non-Natives). Dietary and physical activity information was available for a subset of Cree women (n = 152). RESULTS: Age and pregravid weight were independent predictors of GDM in both Cree and non-Native women. After these predictors were controlled for, normal-weight (</=77 kg) Cree women were not at increased risk of GDM (OR: 1.42; 95% CI: 0.67, 2.71) but overweight Cree women had a higher risk than did overweight non-Native women (OR: 2.25; 95% CI: 1.32, 3.80). CONCLUSIONS: Overweight Cree women are at increased risk of GDM. Given the high prevalence of pregravid overweight among the Cree, the burden of GDM is higher than among non-Native Canadians.

Adult↗

Membrane topology and cellular location of the Treponema pallidum glycerophosphodiester phosphodiesterase (GlpQ) ortholog.

Recent reports that isolated Treponema pallidum outer membranes contain an ortholog for glycerophosphodiester phosphodiesterase (GlpQ) (D. V. Shevchenko, D. R. Akins, E. J. Robinson, M. Li, O. V. Shevchenko, and J. D. Radolf, Infect. Immun. 65:4179-4189, 1997) and that this protein is a potential opsonic target for T. pallidum (C. E. Stebeck, J. M. Shaffer, T. W. Arroll, S. A. Lukehart, and W. C. Van Voorhis, FEMS Microbiol. Lett. 154:303-310, 1997) prompted a more detailed investigation of its physicochemical properties and cellular location. [14C]palmitate radiolabeling studies of a GlpQ-alkaline phosphatase fusion expressed in Escherichia coli confirmed the prediction from DNA sequencing that the protein is lipid modified. Studies using Triton X-114 phase partitioning revealed that the protein's amphiphilicity is due to lipid modification and that a substantial portion of the polypeptide is associated with the T. pallidum peptidoglycan sacculus. Three different approaches, i.e., (i) proteinase K treatment of intact treponemes, (ii) indirect immunofluorescence analysis of treponemes encapsulated in agarose beads, and (iii) opsonophagocytosis of treponemes incubated with antiserum against recombinant GlpQ by rabbit peritoneal macrophages, confirmed that GlpQ is entirely subsurface in T. pallidum. Moreover, rabbits hyperimmunized with GlpQ were not protected against intradermal challenge with virulent treponemes. Circular dichroism spectroscopy confirmed that the recombinant form of the polypeptide lacked discernible evidence of denaturation. Finally, GlpQ was not radiolabeled when T. pallidum outer membranes were incubated with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazarene, a photoactivatable, lipophilic probe which promiscuously labels both proteins and lipids within phospholipid bilayers. Taken as a whole, these studies indicate that the T. pallidum GlpQ ortholog is a periplasmic protein associated predominantly with the spirochete's peptidoglycan-cytoplasmic membrane complex.

Animals↗

Basal cells are progenitors of luminal cells in primary cultures of differentiating human prostatic epithelium.

BACKGROUND: Human prostatic epithelium consists mainly of basal and secretory luminal cells: the origin of these phenotypes from a common stem cell, within the basal compartment, has been proposed but not yet demonstrated. METHODS: Analyses by light and electron microscopy, immunocytochemistry, and flow cytometry were used to determine lineage. The criteria for identifying the different phenotypes were characteristic morphology, and organization and expression of luminal- and basal-specific markers. RESULTS: After organoids attached, outgrowths appeared with cells maintaining close cell-to-cell associations. The dividing cell compartment contained a subpopulation of cells with stem-cell characteristics and a major population that may correspond to amplifying cells. The characteristics of the stem-cell phenotype included reactivity with antibodies CKbasal, CK14, and Ki67. The amplifying cells were characterized as an intermediate phenotype between basal and luminal, as reactivity was demonstrated with CKbasal, CK14, and CK18. As outgrowths eventually merged, multilayering was apparent and cells on the uppermost layer had numerous secretory vacuoles and reacted strongly with antibodies CK18 and CK19, androgen receptor, and prostate-specific antigen, which is characteristic of secretory luminal cells in vivo. In passaged cultures, loss of reactivity with CKbasal was detected; we postulate that this population contains the stem-cell fraction. CONCLUSIONS: These findings demonstrate that basal and luminal cells are of the same lineage and are derived from a common stem cell. Moreover, the progenitor stem cells reside within the basal compartment.

Cell Differentiation↗

Children's mental representation of referential relations.

We identify a surprising discrepancy in children's performance in two tasks which appear superficially to require handling of the same properties of the representational mind. Four- to six-year-olds made judgements about the knowledge of a protagonist who had only partial information about an object: the child knew that an object in a box had two descriptions, X and Y (e.g. dice and eraser), but the protagonist had access to only one of these, X. In Experiment 1, children who passed a standard false-belief task also judged correctly that the protagonist did not know the X was Y, but often judged wrongly that he did know there was a Y in the box. In Experiment 2, children predicted wrongly where the protagonist would look for a Y: the problem was not purely linguistic. We argue that success on standard theory-of-mind tasks can be supported by a more basic representing ability than is assumed in current theories, and that children's mental representation of referential relations between the world and the mind subsequently undergoes important change.

Age Factors↗

'Theory of mind' skills during an acute episode of psychosis and following recovery.

BACKGROUND: A neuropsychological formulation of schizophrenia has suggested that problems with meta-representation underpin both positive and negative symptoms. This study tested Frith's account by asking patients experiencing an acute episode of psychosis to complete a set of tasks that involved Theory of Mind (ToM) skills. METHODS: Fourteen patients who fulfilled criteria for schizophrenia, 10 deluded patients who were suffering from psychotic disorders other than schizophrenia and 12 depressed patients completed second-order false belief tasks, a test which involved substitution of a co-referential term in a linguistic description of an event, and metaphor and irony tasks. The battery of tests was completed during the acute phase and following recovery. Selection of these patient groups allowed comparisons to be made between schizophrenia patients and non-schizophrenia patients and between patients with and without persecutory delusions. RESULTS: Schizophrenia patients, who had a multiplicity of positive and negative symptoms, performed significantly worse than non-schizophrenia patients on some of the ToM tasks during an acute episode. Patients with delusions of persecution and reference did not perform significantly worse than non-deluded patients on ToM tasks. There was no significant difference between groups in performance on any of the tasks at recovery. CONCLUSIONS: The results provide at best weak support for Frith's account and it remains unclear whether the ToM deficits demonstrated are genuine deficits or are a result of information-processing overload. However, it is clear that difficulties interpreting interpersonal contexts, as shown by some schizophrenia patients, are state rather than trait characteristics.

Adult↗

Effects of a new 5 alpha reductase inhibitor (epristeride) on human prostate cell cultures.

BACKGROUND: Inhibitors of 5 alpha reductase (5 alpha R), the enzyme that converts testosterone to dihydrotestosterone (DHT), have been shown to retard the growth of hyperplastic prostates. This study evaluates the effects of the 5 alpha R inhibitor, epristeride, on cultured stromal and epithelial cells from benign, hyperplastic adult prostates. METHODS: [3H]-thymidine incorporation was used as a measure of proliferation. Prostate-specific antigen (PSA) was quantified by ELISA and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Stromal cell proliferation in response to testosterone was dose-dependently inhibited by epristeride (1 x 10(-9) -3 x 10(-7) M, P < 0.05). However, epristeride had no effect on DHT-induced growth or the growth of androgen-unresponsive stroma. Upregulation of PSA secretion from epithelial cells by androgens was downregulated by epristeride (3 x 10(-9) M, P < 0.05) in testosterone-treated cells. Transforming growth factor beta-1 (TGF beta-1) secretion was downregulated by testosterone treatment and increased following treatment with epristeride (3 x 10(-9) M, P < 0.05). CONCLUSIONS: This demonstrates that epristeride specifically blocks testosterone-induced effects on prostatic cultures. TGF beta-1 may be a marker of 5 alpha reductase activity.

5-alpha Reductase Inhibitors↗

When speech conflicts with seeing: young children's understanding of informational priority.

In a series of investigations we found that children between 3 and 5 years of age judged that an utterance (such as, "There's milk in the jug") would be ignored by a listener who had previously seen something contradictory (orange juice in the jug). However, children judged that the listener would believe the message "There's milk in the jug" when he had not previously seen inside. In these various conditions, child participants had not seen for themselves what was inside the jug, so it was impossible for their own directly perceived knowledge to contaminate their judgments of what the protagonist believed. Under these conditions, even many false-belief failers did not assume that the listener would believe whatever they themselves thought was true. Moreover, the results of control conditions suggested that children's success could not be attributed to low-level strategies. These results seem to indicate an early understanding of how people prioritize information, with the consequence that they acknowledge that one and the same message would be believed in one context but not in another.

Child, Preschool↗