Models for guidance in kagome-structured hollow-core photonic crystal fibres

We demonstrate by numerical simulation that the general features of the loss spectrum of photonic crystal fibres (PCF) with a kagome structure can be explained by simple models consisting of thin concentric hexagons or rings of glass in air. These easily analysed models provide increased understanding of the mechanism of guidance in kagome PCF, and suggest ways in which the high-loss resonances in the loss spectrum may be shifted. © 2007 Optical Society of America

Optical excitation and characterization of gigahertz acoustic resonances in optical fiber tapers

Transverse acoustic resonances at gigahertz frequencies are excited by electrostriction in the few-micrometer-thick waists of low-loss optical fiber tapers of up to 40 cm long. A pump-probe technique is used in which the resonances are excited by a train of optical pulses and probed in a Sagnac interferometer. Strong radially symmetric acoustic resonances are observed and the dependence of their frequencies on taper thickness is investigated. Such easily reconfigurable acousto-optic interactions may have applications in the high-frequency mode locking of fiber lasers. (C) 2008 American Institute of Physics.931

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Training teachers in classroom management to improve mental health in primary school children: the STARS cluster RCT

This is the final version. Available from NIHR Journals Library via the DOI in this record.Background Poor mental health in childhood is common, persistent and associated with a range of adverse outcomes that include persistent psychopathology, as well as risk-taking behaviour, criminality and educational failure, all of which may also compromise health. There is a growing policy focus on children’s mental health and the role of schools in particular in addressing this. Objectives To evaluate whether or not the Incredible Years® (IY) Teacher Classroom Management (TCM) training improved children’s mental health, behaviour, educational attainment and enjoyment of school, improved teachers’ mental health and relationship with work, and was cost-effective in relation to potential improvements. Design A two-arm, pragmatic, parallel-group, superiority, cluster randomised controlled trial. Setting A total of 80 UK schools (clusters) were recruited in three distinct cohorts between 2012 and 2014 and randomised to TCM (intervention) or teaching as usual [(TAU) control] with follow-ups at 9, 18 and 30 months. Schools and teachers were not masked to allocation. Participants Eighty schools (n = 2075 children) were randomised: 40 (n = 1037 children) to TCM and 40 (n = 1038 children) to TAU. Interventions TCM was delivered to teachers in six whole-day sessions, spread over 6 months. The explicit goals of TCM are to enhance classroom management skills and improve teacher–student relationships. Main outcome measures The primary planned outcome was the teacher-reported Strengths and Difficulties Questionnaire Total Difficulties (SDQ-TD) score. Random-effects linear regression and marginal logistic regression models using generalized estimating equations were used to analyse outcomes. Results The intervention reduced the SDQ-TD score at 9 months [adjusted mean difference (AMD) –1.0, 95% confidence interval (CI) –1.9 to –0.1; p = 0.03] but there was little evidence of effects at 18 months (AMD –0.1, 95% CI –1.5 to 1.2; p = 0.85) and 30 months (AMD –0.7, 95% CI –1.9 to 0.4; p = 0.23). Planned subgroup analyses suggested that TCM is more effective than TAU for children with poor mental health. Cost-effectiveness analysis using the SDQ-TD suggested that the probability of TCM being cost-effective compared with TAU was associated with some uncertainty (range of 40% to 80% depending on the willingness to pay for a unit improvement in SDQ-TD score). In terms of quality-adjusted life-years (QALYs), there was evidence to suggest that TCM was cost-effective compared with TAU at the National Institute for Health and Care Excellence thresholds of £20,000–30,000 per QALY at 9- and 18-month follow-up, but not at 30-month follow-up. There was evidence of reduced disruptive behaviour (p = 0.04) and reductions in inattention and overactivity (p = 0.02) at the 30-month follow-up. Despite no main effect on educational attainment, subgroup analysis indicated that the intervention’s effect differed between those who did and those who did not have poor mental health for both literacy (interaction p = 0.04) and numeracy (interaction p = 0.03). Independent blind observations and qualitative feedback from teachers suggested that teachers’ behaviour in the classroom changed as a result of attending TCM training. Limitations Teachers were not masked to allocation and attrition was marked for parent-reported data. Conclusions Our findings provide tentative evidence that TCM may be an effective universal child mental health intervention in the short term, particularly for primary school children who are identified as struggling, and it may be a cost-effective intervention in the short term. Future work Further research should explore TCM as a whole-school approach by training all school staff and should evaluate the impact of TCM on academic progress in a more thorough and systematic manner.National Institute for Health Research (NIHR

Does Medical Students' Preference of Test Format (Computer-based vs. Paper-based) have an Influence on Performance?

<p>Abstract</p> <p>Background</p> <p>Computer-based examinations (CBE) ensure higher efficiency with respect to producibility and assessment compared to paper-based examinations (PBE). However, students often have objections against CBE and are afraid of getting poorer results in a CBE.</p> <p>The aims of this study were (1) to assess the readiness and the objections of students to a CBE vs. PBE (2) to examine the acceptance and satisfaction with the CBE on a voluntary basis, and (3) to compare the results of the examinations, which were conducted in different formats.</p> <p>Methods</p> <p>Fifth year medical students were introduced to an examination-player and were free to choose their format for the test. The reason behind the choice of the format as well as the satisfaction with the choice was evaluated after the test with a questionnaire. Additionally, the expected and achieved examination results were measured.</p> <p>Results</p> <p>Out of 98 students, 36 voluntarily chose a CBE (37%), 62 students chose a PBE (63%). Both groups did not differ concerning sex, computer-experience, their achieved examination results of the test, and their satisfaction with the chosen format. Reasons for the students' objections against CBE include the possibility for outlines or written notices, a better overview, additional noise from the keyboard or missing habits normally present in a paper based exam. The students with the CBE tended to judge their examination to be more clear and understandable. Moreover, they saw their results to be independent of the format.</p> <p>Conclusions</p> <p>Voluntary computer-based examinations lead to equal test scores compared to a paper-based format.</p

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations are common in myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during the evolution of acute myeloid leukemia (AML), where we observed stage-specific and diametrically opposite functions for Ezh2 at the early and late stages of disease. During disease maintenance, WT Ezh2 exerts an oncogenic function that may be therapeutically targeted. In contrast, Ezh2 acts as a tumor suppressor during AML induction. Transcriptional analysis explains this apparent paradox, demonstrating that loss of Ezh2 derepresses different expression programs during disease induction and maintenance. During disease induction, Ezh2 loss derepresses a subset of bivalent promoters that resolve toward gene activation, inducing a feto-oncogenic program that includes genes such as Plag1, whose overexpression phenocopies Ezh2 loss to accelerate AML induction in mouse models. Our data highlight the importance of cellular context and disease phase for the function of Ezh2 and its potential therapeutic implications.The Huntly laboratory is funded by CRUK (program C18680/ A25508), the European Research Council (grant 647685 COMAL), the Kay Kendall Leukaemia Fund, the Medical Research Council (MRC), Bloodwise, the Wellcome Trust, and the Cambridge National Institute of Health Research Biomedical Research Centre. F. Basheer is a recipient of a Wellcome Trust PhD for Clinicians award. P. Gallipoli is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the Wellcome Trust/ MRC center grant (097922/Z/11/Z) and support from Wellcome Trust strategic award 100140. Research in the laboratory is also supported by core funding from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. This research was supported by the Cambridge National Institute of Health Research Biomedical Research Centre Cell Phenotyping Hub

Predictions for Higgs production at the Tevatron and the associated uncertainties

We update the theoretical predictions for the production cross sections of the Standard Model Higgs boson at the Fermilab Tevatron collider, focusing on the two main search channels, the gluon-gluon fusion mechanism $gg \to H$ and the Higgs-strahlung processes $q \bar q \to VH$ with $V=W/Z$, including all relevant higher order QCD and electroweak corrections in perturbation theory. We then estimate the various uncertainties affecting these predictions: the scale uncertainties which are viewed as a measure of the unknown higher order effects, the uncertainties from the parton distribution functions and the related errors on the strong coupling constant, as well as the uncertainties due to the use of an effective theory approach in the determination of the radiative corrections in the $gg \to H$ process at next-to-next-to-leading order. We find that while the cross sections are well under control in the Higgs--strahlung processes, the theoretical uncertainties are rather large in the case of the gluon-gluon fusion channel, possibly shifting the central values of the next-to-next-to-leading order cross sections by more than $\approx 40$. These uncertainties are thus significantly larger than the $\approx 10$ error assumed by the CDF and D0 experiments in their recent analysis that has excluded the Higgs mass range $M_H=$162-166 GeV at the 95% confidence level. These exclusion limits should be, therefore, reconsidered in the light of these large theoretical uncertainties.Comment: 40 pages, 12 figures. A few typos are corrected and some updated numbers are provide

A comparison of methods for purification and concentration of norovirus GII-4 capsid virus-like particles

Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis worldwide. NoV GII-4 VP1 protein was expressed in a recombinant baculovirus system using Sf9 insect cells. Several methods for purification and concentration of virus-like particles (VLPs) were evaluated. Electron microscopy (EM) and histo-blood group antigen (HBGA) binding assays showed that repeated sucrose gradient purification followed by ultrafiltration resulted in intact VLPs with excellent binding to H type 3 antigens. VLPs were stable for at least 12 months at 4°C, and up to 7 days at ambient temperature. These findings indicate that this method yielded stable and high-quality VLPs