Are two cues always better than one? The role of multiple intra-sensory cues compared to multi-cross-sensory cues in children's incidental category learning.

Simultaneous presentation of multisensory cues has been found to facilitate children's learning to a greater extent than unisensory cues (e.g., Broadbent, White, Mareschal, & Kirkham, 2017). Current research into children's multisensory learning, however, does not address whether these findings are due to having multiple cross-sensory cues that enhance stimuli perception or a matter of having multiple cues, regardless of modality, that are informative to category membership. The current study examined the role of multiple cross-sensory cues (e.g., audio-visual) compared to multiple intra-sensory cues (e.g., two visual cues) on children's incidental category learning. On a computerized incidental category learning task, children aged six to ten years (N = 454) were allocated to either a visual-only (V: unisensory), auditory-only (A: unisensory), audio-visual (AV: multisensory), Visual-Visual (VV: multi-cue) or Auditory-Auditory (AA: multi-cue) condition. In children over eight years of age, the availability of two informative cues, regardless of whether they had been presented across two different modalities or within the same modality, was found to be more beneficial to incidental learning than with unisensory cues. In six-year-olds, however, the presence of multiple auditory cues (AA) did not facilitate learning to the same extent as multiple visual cues (VV) or when cues were presented across two different modalities (AV). The findings suggest that multiple sensory cues presented across or within modalities may have differential effects on children's incidental learning across middle childhood, depending on the sensory domain in which they are presented. Implications for the use of multi-cross-sensory and multiple-intra-sensory cues for children's learning across this age range are discussed.

Incidental category learning and cognitive load in a multisensory environment across childhood.

Multisensory information has been shown to facilitate learning (Bahrick & Lickliter, 2000; Broadbent, White, Mareschal, & Kirkham, 2017; Jordan & Baker, 2011; Shams & Seitz, 2008). However, although research has examined the modulating effect of unisensory and multisensory distractors on multisensory processing, the extent to which a concurrent unisensory or multisensory cognitive load task would interfere with or support multisensory learning remains unclear. This study examined the role of concurrent task modality on incidental category learning in 6- to 10-year-olds. Participants were engaged in a multisensory learning task while also performing either a unisensory (visual or auditory only) or multisensory (audiovisual) concurrent task (CT). We found that engaging in an auditory CT led to poorer performance on incidental category learning compared with an audiovisual or visual CT, across groups. In 6-year-olds, category test performance was at chance in the auditory-only CT condition, suggesting auditory concurrent tasks may interfere with learning in younger children, but the addition of visual information may serve to focus attention. These findings provide novel insight into the use of multisensory concurrent information on incidental learning. Implications for the deployment of multisensory learning tasks within education across development and developmental changes in modality dominance and ability to switch flexibly across modalities are discussed. (PsycINFO Database Record

Methotrexate toxicity during treatment of chronic plaque psoriasis: a case report and review of the literature.

Methotrexate continues to be one of the most widely used systemic immunosuppressive agents in dermatology. In addition to the important, well-characterized adverse effects such as hepatotoxicity and myelosuppression, methotrexate may induce a number of rare cutaneous adverse events including methotrexate-induced ulceration. We present a case of methotrexate-induced cutaneous ulceration in a patient with chronic plaque psoriasis occurring during long-standing methotrexate therapy. Withdrawal of the drug and appropriate skin care led to rapid healing of the ulceration and the agent was later safely reintroduced for the ongoing management of the patient's chronic plaque psoriasis. Review of the literature demonstrates cases of this important rare adverse event, primarily occurring in patients with chronic plaque psoriasis, induced by triggers such as accidental overdose or introduction of an interacting agent. Cutaneous ulceration typically precedes other markers of toxicity. Active treatment with folinic acid (calcium leucovorin) may be required. Early recognition, prompt cessation of methotrexate, and appropriate treatment minimizes morbidity. Dermatologists need to be alert to the possibility of cutaneous adverse events associated with methotrexate therapy, aware of potential drug interactions, and confident in the management of methotrexate toxicity.

Mesenchymal chondrosarcoma of the orbit: an unusual site for a rare tumour.

Mesenchymal chondrosarcoma is a rare tumour with orbital involvement being an exceptional occurrence. We present a case of a 22-year old man with such disease, together with details of his management. A brief literature review of this uncommon tumour was also enclosed.

U.K. guidelines for the management of cutaneous melanoma.

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.

UK guidelines for the management of cutaneous melanoma.

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the UK, they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.

What criteria reliably distinguish melanoma from benign melanocytic lesions?

The differential diagnosis of melanocytic lesions is fraught with difficulty and a common source of litigation either if a lesion misreported as 'benign' recurs locally or re-presents with nodal metastases or if an atypical naevus is called 'malignant' leading to a cosmetically unsatisfactory wider resection, unwarranted anxiety about prognosis and adverse life insurance prospects. Several authors have claimed that there are valid morphological criteria which, alone or in combination, enable reliable distinction between benign and malignant melanocytic lesions. Others question these criteria and, doubting the extent to which unequivocal diagnoses can be rendered in all cases, believe that the diagnosis is purely subjective and that most diagnostic errors are non-negligent. To address these issues, expert opinions were commissioned from three sets of authors. Okun, Edelstein & Kasznica emphasize that a significant minority of melanocytic lesions are so borderline morphologically that diagnostic uncertainty is allowable and that such uncertainty can be handled responsibly. Kirkham, in favouring the methodical use of criteria, concedes that they are 'largely opinion-based rather than evidence-based, but do go beyond mere subjective pattern analysis'. In agreement with Okun and his colleagues. Slater emphasises that no single feature is reliable by itself and that all aspects, including clinical details, should be interpreted together; he has no hesitation in reporting the diagnosis as 'uncertain' in doubtful cases. In the absence of a specific marker pathognomonic of melanocytic malignancy, the diagnosis will continue to rely on the judicious application of morphological criteria with a small proportion of elusive cases in which diagnostic uncertainty should not be concealed.

Early developments in the ability to understand the relation between stimulus and reward.

Delayed nonmatching to sample (DNMS) is used to test the recognition memory function dependent on the medial temporal lobe. Children cannot succeed on this task until about 21 months. Because robust recognition is present well before then, the late emergence of another ability must account for the late success on DNMS. Evidence is presented here that the critical late-maturing competence is the ability to grasp the relation between stimulus and reward--that is, to understand that the stimulus is a symbol or marker for the reward. Infants of 9 and 12 months were tested on 3 conditions of DNMS. A sample object was presented. After a delay, the sample and a novel object appeared; choice of the novel object was rewarded. In the standard task, the reward was in a well beneath the stimulus. In the verbal-reward condition the reward was not a separate object but was praise and applause. In the Velcro condition, the reward, although a separate and separable object, was attached to the base of the stimulus. Most infants at both ages succeeded in the verbal-reward and Velcro conditions but not in the standard condition.

Rule selection versus rule execution in preschoolers: an error-detection approach.

In 2 experiments, an error-detection approach was used to determine whether 3-year-olds' perseverative errors on the postswitch phase of the Dimensional Change Card Sort (DCCS) are due to lack of response control or representational inflexibility. In Experiment 1, 3-, 4-, and 5-year-olds watched a puppet sort perseveratively on the postswitch phase and evaluated its responses. Most 4- and 5-year-olds detected the puppet's perseverative errors, whereas most 3-year-olds failed to do so despite detecting errors on a simpler card sort. Experiment 2 revealed that 3-year-olds who failed to correctly evaluate the puppet's behavior tended to fail their own DCCS. Results imply that perseveration on the DCCS cannot be attributed to difficulty inhibiting prepotent motor responses. Instead, changes in rule use between 3 and 5 years of age are interpreted in terms of the development of representational flexibility.

The value of the polymerase chain reaction in the diagnosis of cutaneous T-cell infiltrates.

The distinction between reactive and neoplastic cutaneous T-cell infiltrates is difficult and requires good clinicopathologic correlation. Many cases manifest changes that are at the borderline between the two. The polymerase chain reaction (PCR) has been reported to detect monoclonality in 52-90% of cutaneous T-cell lymphomas and may be of use in the diagnosis of histologically borderline lesions. We have investigated the use of PCR in a series of borderline lesions including borderline biopsy samples from patients who subsequently developed cutaneous lymphoma. PCR amplification of T-cell receptor (TCR)-gamma chain gene was performed on formalin-fixed, paraffin-embedded tissue from 27 cases of clinically and histologically typical mycosis fungoides (MF), 22 borderline biopsy samples from 10 patients who subsequently developed MF (pre-MF), 32 clinically suspicious, histologically borderline lesions, and 31 cases of chronic dermatitis. Monoclonality was demonstrated in 16 of 27 (59%) cases of MF, 10 of 22 (50%) pre-MF biopsy samples (six of 10 patients), and six of 32 (19%) borderline biopsy samples. The same size monoclonal band was detected in pre-MF biopsy samples from six of seven patients in which a band was demonstrated in the diagnostic MF biopsy. Sequencing confirmed that the MF biopsy sample and the pre-MF biopsy sample contained the same clone. The 31 dermatitis cases gave rise to polyclonal PCR products. Monoclonality can be demonstrated using PCR in 59% of MF cases, which is comparable with other T-cell lymphomas and in up to 50% of borderline biopsy samples in patients who later develop lymphoma. Detection of T-cell monoclonality by PCR is strong evidence of an established or evolving cutaneous T-cell lymphoma.

An immunocytochemical study of MHC class I expression on human Langerhans cells and melanocytes.

Classical MHC class I glycoproteins (HLA-A, B, and C) present endogenous cytosolic peptide antigen fragments to CD8-positive T-cells. CD8-positive T-cell recognition and destruction of virus-infected cells are dependent on adequate cellular MHC class I expression. Constitutive MHC class I expression is ubiquitous, but known to be deficient on specific differentiated cell types which include hepatocytes, neurones, chondrocytes and myocytes. Although enabling assessment of MHC class I expression on individual cells, limitations of immunocytochemistry were encountered with this assessment on Langerhans cells and melanocytes. These dispersed intraepidermal cells were obscured by adjacent keratinocytes in sections immunostained for MHC class I glycoproteins. Initiatives designed to resolve the issue have included immunoelectron microscopy, cell culture techniques, and animal bone marrow chimera models. Despite the elegance of these techniques, the issue of MHC class I expression on Langerhans cells and melanocytes remains unresolved. In this immunocytochemical study, an alternative strategy was based upon the recognized deficiency of epithelial MHC class I expression within pilosebaceous adnexal units. Langerhans cells and melanocytes were therefore studied within this microenvironment of deficient MHC class I expression, using monomorphic and polymorphic MHC markers. Langerhans cells and melanocytes were demonstrated within pilosebaceous units of scalp skin by immunocytochemistry. Differentiation markers OKT6 (CD1a) and TMH1 defined Langerhans cells and melanocytes, respectively. Monomorphic MHC markers W6/32 and TAL IB5 defined invariant epitopes of HLA class I and II, respectively. Polymorphic MHC class I markers defined the HLA-Bw4 and HLA-Bw6 supertypic determinants. Constitutive MHC class I expression was shown to be deficient on Langerhans cells and melanocytes.

Loss of wild-type p53 and C-erbb2 amplification correlates with high-grade breast carcinomas.

Breast cancer is the most common cancer in women in the western world. Two of the most frequently occuring chromosomal abnormalities in human breast carcinoma are the loss of p53 tumour suppressor gene function and the amplification of the c-erbB2 oncogene. Previous studies have demonstrated the role of p53 gene product in the maintenance of chromosomal stability and the correlation between c-erbB2 amplification and breast carcinogenesis. In this study we have examined the existence of a possible correlation between these genetic alterations in a panel of 83 malignant breast tumours (69 adeno and 14 lobular carcinomas). The status of a related gene, c-erbB3, was also examined. With the aid of microsattelite marker TP53CA loss of heterozygosity (LOH) was detected in the p53 locus in 49% of the tumours. Histochemical analysis of 64 of these tumours with the p53 antibody CM1 demonstrated staining, indicative of an elevated steady-state level of p53 protein in 23 rumours (36%). Amplification of the c-erbB2 gene was detected in 20 of 75 tumours analysed (27%). In the tumours with c-erbB2 amplification 12 also had p53 LOH. In at least another 2 tumours there was increased p53 protein level but no LOH. Therefore in 75% of the tumours with c-erbB2 amplification there was evidence of loss of normal p53 function. There was no evidence of c-erbB3 amplification in any of the 75 rumours analysed. The data presented demonstrates a strong correlation between the loss of p53 and tumour grade (p<0.00545), and a strong association between c-erbB2, but not c-erbB3, amplification and loss of p53 (p<0.0170).

The use of cytology in the diagnosis of basal cell carcinoma.

Two hundred and forty patients with basal cell carcinomas (BCCs) on the head or neck were studied. Scrapings of the lesions were taken for cytological examination, and a 3-mm punch biopsy was performed for histopathological study. The accuracy of diagnosis by each method was compared. Both methods confirmed the clinical diagnosis in 226 cases, and both were negative in 10 cases. Cytopathology gave one false negative result (0.42%), and histopathology gave two false negative results (0.83%). Cytopathology gave one false positive result (0.42%), and histopathology did not produce any false positive results. We conclude that cytological examination of skin scrapings from suspected BCCs is a rapid and reliable method of diagnosis.