Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21

BACKGROUND: Down syndrome (DS) is caused by trisomy 21 (+21), but the aberrations in gene expression resulting from this chromosomal aneuploidy are not yet completely understood. METHODS: We used oligonucleotide microarrays to survey mRNA expression in early- and late-passage control and +21 fibroblasts and mid-gestation fetal hearts. We supplemented this analysis with northern blotting, western blotting, real-time RT-PCR, and immunohistochemistry. RESULTS: We found chromosome 21 genes consistently over-represented among the genes over-expressed in the +21 samples. However, these sets of over-expressed genes differed across the three cell/tissue types. The chromosome 21 gene MX1 was strongly over-expressed (mean 16-fold) in senescent +21 fibroblasts, a result verified by northern and western blotting. MX1 is an interferon target gene, and its mRNA was induced by interferons present in +21 fibroblast conditioned medium, suggesting an autocrine loop for its over-expression. By immunohistochemistry the p78(MX1 )protein was induced in lesional tissue of alopecia areata, an autoimmune disorder associated with DS. We found strong over-expression of the purine biosynthesis gene GART (mean 3-fold) in fetal hearts with +21 and verified this result by northern blotting and real-time RT-PCR. CONCLUSION: Different subsets of chromosome 21 genes are over-expressed in different cell types with +21, and for some genes this over-expression is non-linear (>1.5X). Hyperactive interferon signaling is a candidate pathway for cell senescence and autoimmune disorders in DS, and abnormal purine metabolism should be investigated for a potential role in cardiac defects

Food Consumption When Travelling Abroad: Young Chinese Sojourners’ Food Consumption in the UK

This qualitative study investigates the everyday food choices of 21 Chinese sojourners living in two different localities in the UK. Findings from a thematic analysis of semi-structured interviews reveal how participants adopt a food consumption pattern, negotiating between ordinary and extraordinary food choices, including home-made Chinese food, Chinese restaurant food, global brands, British food, to “foods of the world”. Their zooming in and out of different food consumption choices reflects the transformative identity of the sojourners, between their student role during the week and becoming tourists at the weekends, meshing work and tourism during their sojourning in the UK. Theoretically this paper extends the limited understanding of sojourners, showing how their complex food choices reflect their swift transformative identity. Findings also illustrate how consumption patterns adopted by sojourners living in rural areas differ from the ones living in an urban setting

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Preservice training for science teaching and the subsequent classroom practices of teacher-graduates : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University

This study has investigated the effects of a massed and a spaced preservice programme of science training on the subsequent classroom practices of the graduates of these programmes after they had spent 6 months as year-one teachers. The investigation was conducted in 2 phases. Phase 1 entailed an examination of the training presented to the preservice teachers and the instructional behaviours used by the science lecturers during the presentation of training. Phase 2 involved an examination of the classroom practices of the teacher-graduates. The sample for the first phase of the study comprised 5 science lecturers and 120 preservice teachers. For Phase 2 the sample comprised 20 volunteer teachers from the earlier sample, 7 of whom had received spaced curriculum training over a period of 2 years (group 1) and 13 of whom had received massed curriculum training over a period of 6 weeks (group 2). Information gathering techniques included direct observation and audiorecording of the curriculum training sessions and the subsequent science lessons of the 2 groups of teachers, as well as structured interviews and a questionnaire. A system developed by Adams (1965) was used for the analysis of the teaching patterns of both science lecturers and teacher-graduates. The results of the study revealed that both groups of teachers: (i) indicated that they were using 47 competencies presented during preservice training with a "high" mean level of success; (ii) attributed their capability to use such competencies to preservice training, and (iii) reported that the use of these competencies had a "high" mean level of influence on their overall level of success as science teachers. The results also revealed that of the 6 teaching patterns with which they were compared, the averaged teaching patterns of both groups of teachers resembled mostly the actual teaching patterns of their respective lecturers. Moreover, on an individual basis: (i) the (averaged) functional patterns of 15 of the 20 teachers resembled the averaged functional patterns of their respective lecturers; and (ii) the (averaged) structural patterns of 18 of the 20 teachers resembled the averaged structural patterns of their respective lecturers. From this it was concluded that the teachers modelled the teaching patterns of their lecturers. In addition to such findings the following conclusions were drawn from the study: (i) Both massed and spaced enquiry-oriented, science curriculum training did appear to be effective means for ensuring teacher-use of competencies provided during preservice training. (ii) Positive transfer of training did appear to have resulted from programmes of training with the same objectives of the syllabus which the graduates of these programmes subsequently used. (iii) Preservice training in science teaching did effect positive teacher attitudes towards the teaching of science. (iv) Preservice training in science teaching did appear to influence the teachers' own perceptions of how elementary science should be taught. (v) Role modelling did appear to be an effective means of promoting specific teaching behaviours in teachers. (vi) Although teacher-perceptions of the recommendations of their lecturers did appear to influence their own concepts of how science should be taught more than the actual behaviours of their lecturers, the behaviours of their lecturers did appear to have influenced their own teaching patterns more than their own recommendations. (vii) The teachers' ability to control pupils during science classes did appear to have the hightest level of influence on their overall level of success as science teachers. (viii) The teachers' own knowledge and understanding of science did appear to be less influential on their science teaching success than was their own ability to teach whatever science they knew

Orthoptera in the early stages of post-arable rewilding in south-east England

The ideal aim of rewilding is to restore natural processes to create ‘self-willed’ ecosystems involving the creation of large areas of habitat subject to stochastic disturbance, connected by favorable corridors for species to disperse along. Reversion of arable farmland to grassland and scrub habitats on Black Bourn Valley nature reserve in Suffolk (south-east England) through non-intervention allowed succession to occur largely unmanaged. Fields in the early stages of rewilding (4–14 years) are found at Black Bourn Valley, while pond creation has been extensive since 2010, creating water edge habitat and heterogeneity to the re-establishing grassland. Monitoring of Orthoptera revealed statistical evidence that species diversity/richness and field grasshopper Chorthippus brunneus (Thunberg, 1815), meadow grasshopper Pseudochorthippus parallelus (Zetterstedt, 1821), common groundhopper Tetrix undulata (Sowerby, 1806) and slender groundhopper Tetrix subulata (Linnaeus, 1758) were in higher abundance in fields ≥8 years since arable cropping ceased compared to those 4 years post reversion. Fields ≥8 years old were probably favorable due to the presence of microhabitats for basking and egg-laying orthopterans that included ant hills, sparsely vegetated pond edge and open swards with an abundance of fine-leaved grasses (Agrostis and Festuca spp.) and a low abundance of leaf litter. Lagomorph grazing by wild brown hare Lepus europaeus and rabbit Oryctoloagus cuniculus was critical in maintaining exposed soil for Orthoptera in the older fields, while deer paths appeared to create microhabitats that may be utilized by Orthoptera. We postulate that rewilding schemes on arable farmland should use a Rewilding Max approach and avoid the frequent usage of domestic livestock, relying on wild lagomorph and ungulate grazers to maintain an open mosaic habitat structure with only intermittent cattle, horse, or sheep grazing

Power calculations for detecting interaction in stratified 2x2 tables

Given several 2x2 contingency tables, the first step in epidemiologic research is to test for homogeneity of odds ratios across these tables. A second problem of equal interest, but often overlooked, is to evaluate the power of detection of interaction if it is present. We address the latter issue in the context of 2x2 contingency tables. For the 2x2x2 case, given the marginal totals and the odds ratios for the respective two tables, we provide a closed form power formula for the rejection of the null hypothesis of homogeneity of the odds ratios. For several 2x2 tables, we provide a resampling approach to assessing the power for detecting interaction, if present.Woolfs test Breslow-Day test Mantel-Haenszel test Logit model Polish migrant study