Surface Enhanced Second Harmonic Generation from Macrocycle, Catenane, and Rotaxane Thin Films: Experiments and Theory

Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest degree of order is observed in the case of macrocycle monolayers and the lowest in the case of rotaxane multilayers. The second harmonic generation activity is interpreted in terms of electric field induced second harmonic (EFISH) generation where the electric field is created by the substrate silver atoms. The measured second order nonlinear optical susceptibility for a rotaxane thin film is compared with that obtained by considering only EFISH contribution to SHG intensity. The electric field on the surface of a silver layer is calculated by using the Delphi4 program for structures obtained with TINKER molecular mechanics/dynamics simulations. An excellent agreement is observed between the calculated and the measured SHG susceptibilities.

A complete sample of 21-cm absorbers at z~1.3: Giant Metrewave Radio Telescope Survey Using MgII Systems

We present the results of a systematic Giant Metrewave Radio Telescope (GMRT) survey of 21-cm absorption in a representative and unbiased sample of 35 strong MgII systems in the redshift range: zabs~1.10-1.45, 33 of which have W_r>1 \AA. The survey using ~400hrs of telescope time has resulted in 9 new 21-cm detections and stringent 21-cm optical depth upper limits (median 3-sigma optical depth per 10 km/s of 0.017) for the remaining 26 systems. This is by far the largest number of 21-cm detections from any single survey of intervening absorbers. Prior to our survey no intervening 21-cm system was known in the above redshift range and only one system was known in the redshift range 0.7<z<1.5. We discuss the relation between the detectability of 21-cm absorption and various properties of UV absorption lines. We show that if MgII systems are selected with the following criteria, MgII doublet ratio <1.3 and W_r(MgI)/W_r(MgII)>0.3, then a detection rate of 21-cm absorption up to 90% can be achieved. We estimate n_{21}, the number per unit redshift of 21-cm absorbers with W_r(Mg(II)>W_o and integrated optical depth Tau_{21}>Tau_o and show that n_{21} decreases with increasing redshift. In particular, for W_o=1.0 \AA and Tau_o>0.3 km\s, n_{21} falls by a factor 4 from =0.5 to =1.3. The evolution seems to be stronger for stronger MgII systems. Using a subsample of systems for which high frequency VLBA images are available, we show that the effect is not related to the structure of the background radio sources and is most probably due to the evolution of the cold neutral medium filling factor in MgII systems. We find no correlation between the velocity spread of the 21-cm absorption feature and W_r(MgII) at z~1.3.Comment: 22 pages, 8 tables, 12 figures, accepted for publication in MNRA

Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity

Estimating the NIH Efficient Frontier

Background: The National Institutes of Health (NIH) is among the world’s largest investors in biomedical research, with a mandate to: “…lengthen life, and reduce the burdens of illness and disability.” Its funding decisions have been criticized as insufficiently focused on disease burden. We hypothesize that modern portfolio theory can create a closer link between basic research and outcome, and offer insight into basic-science related improvements in public health. We propose portfolio theory as a systematic framework for making biomedical funding allocation decisions–one that is directly tied to the risk/reward trade-off of burden-of-disease outcomes. Methods and Findings: Using data from 1965 to 2007, we provide estimates of the NIH “efficient frontier”, the set of funding allocations across 7 groups of disease-oriented NIH institutes that yield the greatest expected return on investment for a given level of risk, where return on investment is measured by subsequent impact on U.S. years of life lost (YLL). The results suggest that NIH may be actively managing its research risk, given that the volatility of its current allocation is 17% less than that of an equal-allocation portfolio with similar expected returns. The estimated efficient frontier suggests that further improvements in expected return (89% to 119% vs. current) or reduction in risk (22% to 35% vs. current) are available holding risk or expected return, respectively, constant, and that 28% to 89% greater decrease in average years-of-life-lost per unit risk may be achievable. However, these results also reflect the imprecision of YLL as a measure of disease burden, the noisy statistical link between basic research and YLL, and other known limitations of portfolio theory itself. Conclusions: Our analysis is intended to serve as a proof-of-concept and starting point for applying quantitative methods to allocating biomedical research funding that are objective, systematic, transparent, repeatable, and expressly designed to reduce the burden of disease. By approaching funding decisions in a more analytical fashion, it may be possible to improve their ultimate outcomes while reducing unintended consequences

From ‘shallow’ to ‘deep’ policing:‘crash-for-cash’ insurance fraud investigation in England and Wales and the need for greater regulation

The policing of insurance fraud has traditionally been dealt with beyond the criminal justice system as a private matter between the claimant and the insurer with only a few iconic cases referred to the criminal justice system each year. The growth of insurance fraud, particularly ‘crash-for-cash’ fraud, and the disinterest of the police, has led to a change in the response of the insurance industry. This paper will argue that this response can be characterised as a shift from the traditional ‘shallow’ to a ‘deeper’ form of policing which sees greater focus upon criminal and quasi-criminal outcomes. This paper explores some of the private and innovative methods the industry has developed and illustrates what greater private criminal investigation might look like at a time when police privatisation has become a higher profile issue. The paper argues the shift to ‘deeper’ policing necessitates greater regulation of the private investigation of crime and outlines a number of proposals to address this gap which require further consideration and debate

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

A high resolution foreground model for the MWA EoR1 field : model and implications for EoR power spectrum analysis

This article has been published in a revised form in Publications of the Astronomical Society of Australia https://doi.org/10.1017/pasa.2017.26 This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. Under embargo. Embargo end date: 10 February 2018. © Astronomical Society of Australia 2017.The current generation of experiments aiming to detect the neutral hydrogen signal from the Epoch of Reionisation (EoR) is likely to be limited by systematic effects associated with removing foreground sources from target fields. In this paper we develop a model for the compact foreground sources in one of the target fields of the MWA's EoR key science experiment: the `EoR1' field. The model is based on both the MWA's GLEAM survey and GMRT 150 MHz data from the TGSS survey, the latter providing higher angular resolution and better astrometric accuracy for compact sources than is available from the MWA alone. The model contains 5049 sources, some of which have complicated morphology in MWA data, Fornax A being the most complex. The higher resolution data show that 13% of sources that appear point-like to the MWA have complicated morphology such as double and quad structure, with a typical separation of 33~arcsec. We derive an analytic expression for the error introduced into the EoR two-dimensional power spectrum due to peeling close double sources as single point sources and show that for the measured source properties, the error in the power spectrum is confined to high $k_\bot$ modes that do not affect the overall result for the large-scale cosmological signal of interest. The brightest ten mis-modelled sources in the field contribute 90% of the power bias in the data, suggesting that it is most critical to improve the models of the brightest sources. With this hybrid model we reprocess data from the EoR1 field and show a maximum of 8% improved calibration accuracy and a factor of two reduction in residual power in $k$-space from peeling these sources. Implications for future EoR experiments including the SKA are discussed in relation to the improvements obtained.Peer reviewedFinal Accepted Versio

Supermarket/Hypermarket Opportunistic Screening for Atrial Fibrillation (SHOPS-AF) using sensors embedded in the handles of supermarket trolleys: A feasibility study

Background Atrial fibrillation (AF) increases the risk of death, stroke, heart failure, cognitive decline, and healthcare costs but is often asymptomatic and undiagnosed. There is currently no national screening programme for AF. The advent of validated hand-held devices allows AF to be detected in non-healthcare settings, enabling screening to be undertaken within the community. Method and Results In this novel observational study, we embedded a MyDiagnostick single lead ECG sensor into the handles of shopping trolleys in four supermarkets in the Northwest of England: 2155 participants were recruited. Of these, 231 participants either activated the sensor or had an irregular pulse, suggesting AF. Some participants agreed to use the sensor but refused to provide their contact details, or consent to pulse assessment. In addition, some data were missing, resulting in 203 participants being included in the final analyses. Fifty-nine participants (mean age 73.6 years, 43% female) were confirmed or suspected of having AF; 20 were known to have AF and 39 were previously undiagnosed. There was no evidence of AF in 115 participants and the remaining 46 recordings were non-diagnostic, mainly due to artefact. Men and older participants were significantly more likely to have newly diagnosed AF. Due to the number of non-diagnostic ECGs (n=46), we completed three levels of analyses, excluding all non-diagnostic ECGs, assuming all non-diagnostic ECGs were masking AF, and assuming all non-diagnostic ECGs were not AF. Based on the results of the three analyses, the sensor’s sensitivity (95% CI) ranged from 0.70 - 0.93; specificity from 0.15 - 0.97; positive predictive values (PPV) and negative predictive values (NPV) ranged from 0.24 - 0.56 and 0.55-1.00, respectively. These values should be interpreted with caution, as the ideal reference standard on 1934 participants was imperfect. onclusion The study demonstrates that the public will engage with AF screening undertaken as part of their daily routines using hand-held devices. Sensors can play a key role in identifying asymptomatic patients in this way, but the technology must be further developed to reduce the quantity of non-diagnostic ECGs