Donor type microchimerism is an infrequent event following liver transplantation and is not associated with graft acceptance

<p>Donor-type microchimerism, the presence of a minority population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mechanism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with respect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duodenum in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is independent of microchimerism.</p>

Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

<p>People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.</p>

The obligation to provide information where valid consent is not needed

Accounts of consent in medical ethics typically assume that consent plays the same role irrespective of the type of treatment. In this paper I argue that this assumption is false. Because of this, obligations to provide information to patients that stem from the need for consent to be valid will not apply to all types of treatment. This does not mean that there are no reasons to provide such information. The second part of the paper maps out what these reasons are and argues that they are grounded in the obligation of beneficence and a duty to warn, not in considerations of respect for autonomy.

Tacrolimus is not associated with gingival overgrowth in renal transplant patients

<p>BACKGROUND: Cyclosporin A is used extensively to prevent the rejection of allogenic renal transplants. However, it is associated with a variety of undesirable side effects including gingival overgrowth. Tacrolimus (FK506), has been marketed as an effective alternative immunosuppressant to cyclosporin A and recent subjective reports suggest patients taking it complain infrequently of gingival problems. This clinical investigation was undertaken to confirm whether or not tacrolimus adversely affected the gingival health of renal transplant recipients.</p><p>METHODS: Renal transplant patients (RTPs) under the care of the Renal Transplantation Service at the Manchester Royal Infirmary, who had received a renal allograft at least 18 months earlier, were recruited for this study. All but one of the RTPs had been taking tacrolimus since transplantation. The other had commenced tacrolimus therapy two months after receiving her allograft. A hospital based control group was recruited from non transplanted individuals attending the Turner Dental School, Manchester. Each patient underwent a detailed dental assessment and had dental impressions taken. The extent of gingival overgrowth was determined from plaster models.</p><p>RESULTS: 25 renal transplant recipients and 26 control patients were included in the study. None of the individuals in either the tacrolimus or control groups had clinically significant overgrowth. The patients in the tacrolimus group with the highest overgrowth scores were those also taking calcium antagonists as treatment for hypertension.</p><p>CONCLUSION: This study demonstrates that tacrolimus has no adverse effects on the gingival tissues and thus has potential as an alternative immunosuppressant for individuals susceptible to developing cyclosporin A-induced gingival overgrowth.</p>

Is Our Students Learning - QuestionMark: Extending E-Assessment Systems for Adapative Marking and Feedback

Our key contribution is a flexible, automated marking system that adds desirable functionality to existing E-Assessment systems. In our approach, any given E-Assessment system is relegated to a data-collection mechanism, whereas marking and the generation and distribution of personalised per-student feedback is handled separately by our own system. This allows content-rich Microsoft Word feedback documents to be generated and distributed to every student simultaneously according to a per-assessment schedule. <br/><br/>The feedback is adaptive in that it corresponds to the answers given by the student and provides guidance on where they may have gone wrong. It is not limited to simple multiple choice which are the most prescriptive question type offered by most E-Assessment Systems and as such most straightforward to mark consistently and provide individual per-alternative feedback strings. It is also better equipped to handle the use of mathematical symbols and images within the feedback documents which is more flexible than existing E-Assessment systems, which can only handle simple text strings.<br/><br/>As well as MCQs the system reliably and robustly handles Multiple Response, Text Matching and Numeric style questions in a more flexible manner than Questionmark: Perception and other E-Assessment Systems. It can also reliably handle multi-part questions where the response to an earlier question influences the answer to a later one and can adjust both scoring and feedback appropriately.<br/><br/>New question formats can be added at any time provided a corresponding marking method conforming to certain templates can also be programmed. Indeed, any question type for which a programmatic method of marking can be devised may be supported by our system. Furthermore, since the student���s response to each is question is marked programmatically, our system can be set to allow for minor deviations from the correct answer, and if appropriate award partial marks.<br/>

���It is through others that we become ourselves.��� A study of Vygotskian play in Russian and Irish schools.

50 years after publishing his seminal work on play and its role in child development, Vygotskian theory is still highly influential in education, and particularly in early years. This paper presents two examples of full integration of Vygotskian principles into schools in two very different settings. Both report improvements in learning and in well-being, and exemplify the theory-practice-theory cycle, highlighting the development of new theoretical constructs arising out of putting theory firmly into practice. In both settings, the positive results have come from years of effort, in which school personnel who may have been skeptical at first, have been inspired by the impact of adopting Vygotskian play on the children they teach. The Northern Ireland study shows that at least some of the Golden Key principles (mixed-age play and enhanced home-school links) translate perfectly into very different cultural-historical contexts.

Siblings��� Sex is linked to Mental Rotation Performance in Males but not Females

Research has consistently found sex differences in mental rotation. Twin research has suggested that females with male co-twins perform better than females with female co-twins on mental rotation. Because twins share both pre-natal and post-natal environments, it is not possible to test whether this advantage is due to in-uterine transmission of testosterone from males to females or due to socialisation processes. The present study explored whether the advantage of females with brothers can be observed in non-twin siblings. Participants (N = 1799) were assessed on mental rotation. The observed group differences were overall small: males performed significantly better than females; females with sisters performed similarly to females with brothers; importantly, males with brothers performed significantly better than both female groups. The results suggest that sex differences in mental rotation are driven by the group of males with brothers.

Plasma Homocysteine Is Not Subject to Seasonal Variation.

Background: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements. Methods: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season. Results: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97). Conclusions: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual���s average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population.

Monkey and humans exhibit similar motion-processing mechanisms

Single cell recording studies have resulted in a detailed understanding of motion-sensitive neurons in non-human primate visual cortex. However, it is not known to what extent response properties of motion-sensitive neurons in the non-human primate brain mirror response characteristics of motion-sensitive neurons in the human brain. Using a motion adaptation paradigm, the direction aftereffect, we show that changes in the activity of human motion-sensitive neurons to moving dot patterns that differ in dot density bear a strong resemblance to data from macaque monkey. We also show a division-like inhibition between neural populations tuned to opposite directions, which also mirrors neural-inhibitory behaviour in macaque. These findings strongly suggest that motion-sensitive neurons in human and non-human primates share common response and inhibitory characteristics.

Horowitz���s Theory of Ethnic Party Competition and the Case of the SDLP, 1970-79

Donald Horowitz's theory of ethnic conflict suggests that a political party operating in a deeply divided society can be effected by a centrifugal pull even when it is not subject to formal electoral competition. This idea can be applied to Northern Ireland's SDLP in the 1970s, when the party faced no credible electoral rival within its primary political constituency. Doing so helps to explain why the SDLP failed in its original objective of mobilizing a cross-community constituency, and instead became what Horowitz terms an ���ethnically based party,��� representing the interests of only one side of the political divide in Northern Ireland.