BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Systemic lupus erythernatosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to 13 cells. Transgenic (Tg) mice over-expressing the cytokine 13 cell-activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require 13 cell-intrinsic signals through the Toll-like receptor (TLR)-associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in 13 cell responses to T cell-independent antigens. Moreover, BAFF enhanced TLR7/9 expression on 13 cells and TLR-mediated production of autoantibodies. Therefore, autoirnmunity in BAFF Tg mice results from altered 13 cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease

Medical students' perceptions of their development of ‘soft skills' Part II : The development of ‘soft skills' through ‘guiding and growing'

BackgroundThis paper reports on medical students' views on the ways in which their ‘soft skills' were developed. It is the result of a study on soft skills among two groups of students before and after curriculum reform at the School of Medicine of the University of Pretoria. One of the aims of the reform was to provide more teaching and learning opportunities for the development of soft skills. Soft skills include professional interpersonal and social skills, communication skills, and professional and ethical attitudes.MethodsAs symbolic interactionism was used as the theoretical framework to guide the research, qualitative methods were used to collect the data. A purposive-theoretical sample of 42 final-year medical students from the traditional curriculum and 49 from the reformed curriculum was recruited. Data were collected by means of focus groups, individual in-depth interviews and autobiographical sketches. ResultsThe same categories of comments emerged from the data collected from the study participants from both the traditional and the reformed curriculum. The students ascribed their behaviour related to soft skills to personality and innate features. They had varying opinions on whether soft skills could be taught, but there was as a strong feeling that teaching should focus on principles and guidelines for dealing with difficult situations. They believed that, in the end, they should take responsibility for their own development of soft skills. Most participants felt they could at least grow through exposure to teaching activities and the observation of role models. They also indicated that they had developed their soft skills and constructed their own identity through their interaction with others. Their definition of situations was shaped by their interactions with doctors and educators, fellow students and other health professionals. Interaction with patients was considered the most important. For both groups of students their third year was a watershed, as it is the first year of more intensive patient contact and the beginning of serious learning from interaction with patients. The views on the development of soft skills differed very little between the traditional and reformed curriculum groups, except that students who had followed the reformed curriculum felt more prepared through the increased teaching and training efforts. Further consideration needs to be given to the intention of the changed curriculum compared to the actual effect. The way in which the participants in the study described their development of soft skills could be categorised as a complex interplay between ‘being' and ‘becoming'. Instead of using the word ‘acquisition' of soft skills, ‘development' seemed to be more appropriate. The metaphor of ‘guiding' and ‘growing' also captures the development of these skills better than the terms ‘teaching' and ‘learning'.ConclusionTeaching activities in the clinical years should be adapted with a view to facilitating the students' professional growth. New models for the development of medical educators should be created and institutional barriers should be investigated.For full text, click here: SA Fam Pract 2006;48(8):15-15

The conceptualisation of "soft skills" among medical students before and after curriculum reform

Objective: This paper reports on the conceptualisation of "soft skills" as part of a study carried out among two groups of undergraduate medical students before and after curriculum reform at the School of Medicine of the University of Pretoria. Congruent with a call from the World Psychiatric Association, the curriculum reform that was undertaken aimed, inter alia, to place more emphasis on soft skills, including professional interpersonal and social skills, communication skills, and professional and ethical attitudes. Methods: Qualitative methods were used to arrive at a descriptive comparison of the conceptualisation of soft skills by final-year medical students of the traditional curriculum with those of final-year students who had followed the reformed curriculum. A purposive-theoretical sampling method was followed; 42 students from the traditional curriculum and 49 from the reformed curriculum were sampled. Data were collected from seven focus groups, 16 individual interviews, and 23 essays (autobiographical sketches). Results: Both groups of students revealed conceptualisations of soft skills that were similar in kind. The themes they pinpointed were the doctor-patient relationship; relationships with other professionals; being a good listener; explaining things to patients; using good communication skills; establishing rapport with patients from different cultural backgrounds; having a professionally correct attitude; being really interested in patients' well being; having empathy; coping with patients, managing difficult situations, and being ethical and professional. However, the traditional curriculum students offered fewer examples and described fewer experiences that exemplified their soft skills. Students following the reformed curriculum gave rich accounts of their conceptualisation in terms of their own experiences and practical examples of how soft skills had been or could be used, particularly in difficult interpersonal situations. Moreover, they came up with helpful ways of dealing with difficult situations, which surpassed the suggestions offered by the students following the traditional curriculum. Conclusion: The educational and training efforts of the reformed curriculum are associated with an adeptness on the part of the students at applying soft skills to the demands of difficult clinical situations. Keywords: soft skills, interpersonal skills, doctor-patient relationship, professional socialisation South African Psychiatry Review Vol. 9(1) 2006: 33-3

Medical students on the value of role models for developing 'soft skills' - "That's the way you do it

Objective: The Soft Skills Project examined the professional development of medical students at the University of Pretoria, especially their doctor-patient interaction skills and professional socialisation. This paper reports on one of the findings of the project, namely the importance that medical students attach to role models in the development of soft skills. Methods: We used a qualitative method with symbolic interactionism and grounded theory as framework. Fourty two final-year students from the last cohort following the traditional curriculum at the University of Pretoria in 2001, and 49 final years from the first cohort following the reformed curriculum in 2002 were recruited. Data were collected by applying focus groups, in-depth, individual interviews, as well as autobiographical sketches. Data were captured by means of audio tape recordings, transcripts of the tapes, researchers' field notes, and written accounts by students, and were analysed by using a general inductive approach. Results: There were no striking differences between the comments of the two groups. Students considered registrars to be the most influential role models in the clinical teaching context, followed by specialist consultants. Their idea of a good role model was a clinically and academically competent doctor that cared about patients, had good interpersonal skills, and who could inspire students. Students needed and appreciated good role models to help them to develop their own soft skills. They expected guidance and behavioural examples from clinical teachers. Although there were competent role models, the students were exposed to poor role models. Poor role models mainly affect students negatively. Students tend to imitate and perpetuate unacceptable behaviour. Furthermore, poor role models have a negative emotional effect on students and are detrimental to their moral and learning environment. Sometimes, poor role models have a paradoxical positive effect in the sense that they inform students how not to behave. Conclusion: Medical schools and medical doctors working with medical students should be consciously aware of the importance of role models both when allocating clinical teachers to students, and while performing duties with students. It is especially necessary to realise that poor role modelling has important detrimental effects on students. Therefore, an attempt should be made to ensure that not only clinical examination skills, but also soft skills, are demonstrated at the bedside. Measures to ensure adequate exposure of students to positive role models could include: staff development; the identification of good role models to guide registrars; and a reallocation of tasks, where possible, to increase the exposure of students to the ‘natural' role models. Keywords: soft skills, role models, medical students, professionalism South African Psychiatry Review Vol. 9(1) 2006: 28-3

Pathological and ecological host consequences of infection by an introduced fish parasite

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite

Interpreting planners' talk about change: An exploratory study.

Talk by planners about major changes (‘reform’) in a particular planning regime is the focus of this article. Change in planning in the United Kingdom has been a recurrent theme in planning practice and research. However, there is little looking at practitioners both in the public and the private sectors in relation to change. Also, theory development has been limited and the interpretive link between institutional change, organisational change and planners’ situated agency could be strengthened. This article aims to add new dimensions to the current debate by looking at planners in both the public and the private sectors in Wales; by adopting a more open-ended approach requiring planners to generate ideas and display a perspective on planning; and by linking theories of institutional and organisational change with the model of actors’ agency developed by Bevir and Rhodes to form an interpretive frame. With reflections stemming from an exploratory case in Wales, the article seeks also to contribute to debates on planning in the United Kingdom and beyond, reaching to new-institutionalist theory and interpretive ontologie

A multi-disciplinary education process related to the discharging of children from hospital when the child has been diagnosed with type 1 diabetes - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Worldwide, insulin-dependent type 1 diabetes is one of the most frequently diagnosed long-term endocrine disorders found in children and the incidences of this diseased is still increasing. In Sweden the routines are, according to national guidelines, when the child is diagnosed with type 1 diabetes, the child and its family remains at the hospital for about two weeks. There is limited knowledge about how a diabetes team handles a child and its family from admission to discharge, therefore the purpose of this study was to seek a deeper understanding of how the diabetes team's parent/child education process works, from admission to discharge, among families with a child newly diagnosed with type 1 diabetes.</p> <p>Methods</p> <p>Qualitative data collection was used. Four focus-group interviews, with a sample of three diabetes teams from different paediatric hospitals in the south western part of Sweden, were conducted and the data recorded on tape and then analysed using qualitative content analysis.</p> <p>Results</p> <p>The results indicate that achieving a status of self-care on the part of the patient is the goal of the diabetes education programme. Part of the programme is aimed at guiding the child and its parents towards self-help through the means of providing them with knowledge of the disease and its treatment to enable the whole family to understand the need for cooperation in the process. To do this requires an understanding, by the diabetes team, of the individualities of the family in order to gain an overall picture.</p> <p>Conclusion</p> <p>The results of this study show that the diabetes education programme is specifically designed for each family using the internationally recommended clinical practice guidelines with its specific aims and objectives. Achieving the families' willingness to assist in the self-care of the child care is the goal of the parent education process. To achieve this, the paediatric diabetes specialist nurse and the diabetes specialist paediatrician immediately and deliberately start the process of educating the family using a programme designed to give them the necessary knowledge and skills they will need to manage their child's type 1 diabetes at home.</p

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Research misconduct in the fields of ethics and philosophy: researchers’ perceptions in Spain

This is the Author’s Original Manuscript (AOM) (also called a “preprint”) sent to review to Science and Engineering Ethics on 11/10/2020. The final version of the article was published online at SEE on 21/01/2021. The online version is available at: https://doi.org/10.1007/s11948-021-00278-wEmpirical studies have revealed a disturbing prevalence of research misconduct in a wide variety of disciplines, although not, to date, in the areas of ethics and philosophy. This study aims to provide empirical evidence on perceptions of how serious a problem research misconduct is in these two disciplines in Spain, particularly regarding the effects that the model used to evaluate academics’ research performance may have on their ethical behaviour. The methodological triangulation applied in the study combines a questionnaire, a debate at the annual meeting of scientific association, and in-depth interviews. Of the 541 questionnaires sent out, 201 responses were obtained (37.1% of the total sample), with a significant difference in the participation of researchers in philosophy (30.5%) and in ethics (52.8%); 26 researchers took part in the debate and 14 interviews were conducted. The questionnaire results reveal that 91.5% of the respondents considered research misconduct to be on the rise; 63.2% considered at least three of the fraudulent practices referred to in the study to be commonplace, and 84.1% identified two or more such practices. The researchers perceived a high prevalence of duplicate publication (66.5%) and self-plagiarism (59.0%), use of personal influence (57.5%) and citation manipulation (44.0%), in contrast to a low perceived incidence of data falsification or fabrication (10.0%). The debate and the interviews corroborated these data. Researchers associated the spread of these misconducts with the research evaluation model applied in Spain

High Diversity at PRDM9 in Chimpanzees and Bonobos

BACKGROUND: The PRDM9 locus in mammals has increasingly attracted research attention due to its role in mediating chromosomal recombination and possible involvement in hybrid sterility and hence speciation processes. The aim of this study was to characterize sequence variation at the PRDM9 locus in a sample of our closest living relatives, the chimpanzees and bonobos. METHODOLOGY/PRINCIPAL FINDINGS: PRDM9 contains a highly variable and repetitive zinc finger array. We amplified this domain using long-range PCR and determined the DNA sequences using conventional Sanger sequencing. From 17 chimpanzees representing three subspecies and five bonobos we obtained a total of 12 alleles differing at the nucleotide level. Based on a data set consisting of our data and recently published Pan PRDM9 sequences, we found that at the subspecies level, diversity levels did not differ among chimpanzee subspecies or between chimpanzee subspecies and bonobos. In contrast, the sample of chimpanzees harbors significantly more diversity at PRDM9 than samples of humans. Pan PRDM9 shows signs of rapid evolution including no alleles or ZnFs in common with humans as well as signals of positive selection in the residues responsible for DNA binding. CONCLUSIONS AND SIGNIFICANCE: The high number of alleles specific to the genus Pan, signs of positive selection in the DNA binding residues, and reported lack of conservation of recombination hotspots between chimpanzees and humans suggest that PRDM9 could be active in hotspot recruitment in the genus Pan. Chimpanzees and bonobos are considered separate species and do not have overlapping ranges in the wild, making the presence of shared alleles at the amino acid level between the chimpanzee and bonobo species interesting in view of the hypothesis that PRDM9 plays a universal role in interspecific hybrid sterility