Effects of deleting cannabinoid receptor-2 on mechanical and material properties of cortical and trabecular bone

Acknowledgements We thank Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis. Funding ABK was funded by a University of Aberdeen, Institute of Medical Sciences studentship and the Overseas Research Students Awards Scheme.Peer reviewedPublisher PD

Mechanical and material properties of cortical and trabecular bone from cannabinoid receptor-1-null (Cnr1-/-) mice

Funding ABK was funded by a studentship from the University of Aberdeen, Institute of Medical Sciences, and the Overseas Research Students Awards Scheme Acknowledgments We are grateful to Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis.Peer reviewedPostprin

Atomic layer etching of SiO2 with Ar and CHF 3 plasmas: A self-limiting process for aspect ratio independent etching

With ever increasing demands on device patterning to achieve smaller critical dimensions, the need for precise, controllable atomic layer etching (ALE) is steadily increasing. In this work, a cyclical fluorocarbon/argon plasma is successfully used for patterning silicon oxide by ALE in a conventional inductively coupled plasma tool. The impact of plasma parameters and substrate electrode temperature on the etch performance is established. We achieve the self-limiting behavior of the etch process by modulating the substrate temperature. We find that at an electrode temperature of −10°C, etching stops after complete removal of the modified surface layer as the residual fluorine from the reactor chamber is minimized. Lastly, we demonstrate the ability to achieve independent etching, which establishes the potential of the developed cyclic ALE process for small scale device patterning

Balancing ion parameters and fluorocarbon chemical reactants for SiO2 pattern transfer control using fluorocarbon-based atomic layer etching

In manufacturing, etch profiles play a significant role in device patterning. Here, the authors present a study of the evolution of etch profiles of nanopatterned silicon oxide using a chromium hard mask and a CHF3/Ar atomic layer etching in a conventional inductively coupled plasma tool. The authors show the effect of substrate electrode temperature, chamber pressure, and electrode forward power on the etch profile evolution of nanopatterned silicon oxide. Chamber pressure has an especially significant role, with lower pressure leading to lower etch rates and higher pattern fidelity. The authors also find that at higher electrode forward power, the physical component of etching increases and more anisotropic etching is achieved. By carefully tuning the process parameters, the authors are able to find the best conditions to achieve aspect-ratio independent etching and high fidelity patterning, with an average sidewall angle of 87° ± 1.5° and undercut values as low as 3.7 ± 0.5% for five trench sizes ranging from 150 to 30 nm. Furthermore, they provide some guidelines to understand the impact of plasma parameters on plasma ion distribution and thus on the atomic layer etching process

Practice architectures and sustainable curriculum renewal

While there are numerous pedagogical innovations and varying forms of professional learning to support change, teachers rarely move beyond the initial implementation of new ideas and policies and few innovations reach the institutionalised stage. Building on both site ontologies and situated learning in communities of practice perspectives, this paper explores the theory of practice architectures to offer a different and legitimate perspective on sustainable curriculum renewal. Specifically, a practice architecture either enables or constrains particular practice and constitutes the construction of practice from semantic (e.g. language), social (e.g. power relations), and physical (e.g. materials) spaces. Through the juxtaposition of practice architectures with an empirical illustration of longer-term pedagogical change, the paper argues that for pedagogical change to be sustained a practice architecture that relates to an innovation’s intended learning outcomes and the contexts in which an innovation can be used needs to be created. Consequently, the theory of practice architectures can guide reform programmes. Curricularists can begin programmes with a pre-planned approach to assist, a) teachers’ understanding of how to use an innovation, and b) the deconstruction and reconstruction of practice architectures to support an innovation’s survival

Antidepressants versus placebo for depression in primary care

Background Concern has been expressed about the relevance of secondary care studies to primary care patients specifically about the effectiveness of antidepressant medication. There is a need to review the evidence of only those studies that have been conducted comparing antidepressant efficacy with placebo in primary care-based samples. Objectives To determine the efficacy and tolerability of antidepressants in patients (under the age of 65 years) with depression in primary care. Search strategy All searches were conducted in September 2007. The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) Controlled Trials Register was searched, together with a supplementary search of MEDLINE, PsycINFO, EMBASE, LILACS, CINAHL and PSYNDEX. Abstracts of all possible studies for inclusion were assessed independently by two reviewers. Further trials were sought through searching the reference lists of studies initially identified and by scrutinising other relevant review papers. Selected authors and experts were also contacted. Selection criteria Studies were selected if they were randomised controlled trials of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults. Older patients (over 65 years) were excluded. Patients had to be recruited from a primary care setting. For continuous outcomes the Hamilton Depression scale of the Montgomery Asberg Scale was requred. Data collection and analysis Data were extracted using data extraction forms by two reviewers independently, with disagreements resolved by discussion. A similar process was used for the validity assessment. Pooling of results was done using Review Manager 5. The primary outcome was depression reduction, based on a dichotomous measure of clinical response, using relative risk (RR), and on a continuous measure of depression symptoms, using the mean difference (MD), with 95% confidence intervals (CI). Main results There were fourteen studies (16 comparisons) with extractable data included in the review, of which ten studies examined TCAs, two examined SSRIs and two included both classes, all compared with placebo. The number of participants in the intervention groups was 1364 and in the placebo groups 919. Nearly all studies were of short duration, typically 6-8 weeks. Pooled estimates of efficacy data showed an RR of 1.24, 95% CI 1.11-1.38 in favour of TCAs against placebo. For SSRIs this was 1.28, 95% CI 1.15 to 1.43.. The numbers needed to treat (NNT) for TCAs ranged from 7 to 16 {median NNT 9} patient expected event rate ranged from 63% to 26% respectively) and for SSRIs from 7 to 8 {median NNT 7} (patient expected event rate ranged from 48% to 42% respectively) . The numbers needed to harm (NNH for withdrawal due to side effects) ranged from 4 to 30 for TCAs (excluding three studies with no harmful events leading to withdrawal) and 20 to 90 for SSRIs. Authors' conclusions Both TCAs and SSRIs are effective for depression treated in primary care. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2009, Issue 3. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.</p

The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15

Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formatio

Exercise Alleviates Lipid-Induced Insulin Resistance in Human Skeletal Muscle–Signaling Interaction at the Level of TBC1 Domain Family Member 4

Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer