Tunable cavity coupling of the zero phonon line of a nitrogen-vacancy defect in diamond

We demonstrate the tunable enhancement of the zero phonon line of a single nitrogen-vacancy color center in diamond at cryogenic temperature. An open cavity fabricated using focused ion beam milling provides mode volumes as small as 1.24 $\mu$m$^3$. In-situ tuning of the cavity resonance is achieved with piezoelectric actuators. At optimal coupling of the full open cavity the signal from individual zero phonon line transitions is enhanced by about a factor of 10 and the overall emission rate of the NV$^-$ center is increased by 40% compared with that measured from the same center in the absence of cavity field confinement. This result is important for the realization of efficient spin-photon interfaces and scalable quantum computing using optically addressable solid state spin qubits.Comment: 11 pages Main Article + 4 pages Supplementary Info Typos fixed from v

Timing of N application and water constraints on N accumulation and juice amino N concentration in Chardonnay grapevines

The amount and timing of nitrogen (N) application to a vineyard is critical for must yeast assimilable nitrogen (YAN) concentrations. YAN concentrations and amino acid profiles are important for the fermentation process and wine composition. Commonly, N is applied at flowering to optimize leaf functioning or after harvest to enhance vine productivity the following season. In this study N was applied at various stages of berry development to determine allocation patterns between vine perennial and annual components and to assess when berry YAN concentrations can best be optimized. Five year old potted 'Chardonnay' vines received ammonium sulfate fertilizer at six different times from full bloom to two weeks before harvest and were also exposed to either full or half irrigation during that period. Reduced water supply resulted in a higher allocation of N to the perennial structures and less to the annual components of the vine. N allocation to the annual components of the vine was greatest when it was applied at full bloom, however allocation to the perennial components was greatest when it was applied after fruit-set to veraison. The timing of N supply had a substantial influence on YAN concentrations, and was highest when N was applied about two weeks after veraison. Low water supply also resulted in higher juice YAN concentrations. The perennial N reserves in the roots were highest under low water supply and when N was applied at veraison, while the allocation to the annual parts was lower under this irrigation regime. The study indicates that timing of N application and the application of water constraints during berry development can impact on N partitioning, while the total amount accumulated by the vine is not altered

Unequal relationships in high and low power distance societies: a comparative study of tutor - student role relations in Britain and China

This study investigated people's conceptions of an unequal role relationship in two different types of society: a high power distance society and a low power distance society. The study focuses on the role relationship of tutor and student. British and Chinese tutors and postgraduate students completed a questionnaire that probed their conceptions of degrees of power differential and social distance/closeness in this role relationship. ANOVA results yielded a significant nationality effect for both aspects. Chinese respondents judged the relationship to be closer and to have a greater power differential than did British respondents. Written comments on the questionnaire and interviews with 9 Chinese academics who had experienced both British and Chinese academic environments supported the statistical findings and indicated that there are fundamental ideological differences associated with the differing conceptions. The results are discussed in relation to Western and Asian concepts of leadership and differing perspectives on the compatibility/incompatibility of power and distance/closeness

Competing associations in six-species predator-prey models

We study a set of six-species ecological models where each species has two predators and two preys. On a square lattice the time evolution is governed by iterated invasions between the neighboring predator-prey pairs chosen at random and by a site exchange with a probability Xs between the neutral pairs. These models involve the possibility of spontaneous formation of different defensive alliances whose members protect each other from the external invaders. The Monte Carlo simulations show a surprisingly rich variety of the stable spatial distributions of species and subsequent phase transitions when tuning the control parameter Xs. These very simple models are able to demonstrate that the competition between these associations influences their composition. Sometimes the dominant association is developed via a domain growth. In other cases larger and larger invasion processes preceed the prevalence of one of the stable asociations. Under some conditions the survival of all the species can be maintained by the cyclic dominance occuring between these associations.Comment: 8 pages, 9 figure

The patient acceptable symptom state for knee pain - a systematic literature review and meta-analysis

Purpose: Knee pain is highly prevalent, most commonly attributed to osteoarthritis in older people, and in younger people often due to internal derangements. Knee pain can be measured using numerical patient-reported outcome measures (PROMs). Several pain measurement questionnaires have been used for OA pain. These questionnaires each purport to measure the participant’s experience of pain, but may address different pain characteristics (recollection over different time periods, pain impact on function, constant or intermittent or other qualitative aspects of pain). Pooling pain data between studies using different PROMs requires demonstration or transformation to ensure that each PROM would give the same value for pain in a single participant. The Patient Acceptable Symptoms State (PASS) indicates a clinical benchmark that permits comparison between PROMs. Current treatments might relieve but often do not eliminate pain, and PASS is the threshold representing pain which a patient would accept for the remainder of their life. We aimed to systematically review PASS thresholds for different pain PROMs used with people with knee pain, and to identify factors that might influence PASS heterogeneity.Methods: We systematically reviewed literature for PASS scores in knee pain using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, and SPORTDiscus databases from their inception date up to June 2020. PROMs of interest were pain-specific questionnaires (or their related domains). Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Outcome scores were standardised and included in meta-analysis models as a 0-100 scale (0: no pain, 100: highest pain severity). Based on a-priori hypotheses (PROMs, diagnoses, interventions, follow-up timepoints and methodological quality) and following review of data from included studies (PASS score derivation methods), potential effects of study and patient characteristics on PASS were explored. Post-hoc meta-regression explored the relationship between baseline pain and PASS scores. The significance of differences observed between subgroups was evaluated via a Cochran's Q-test. Study heterogeneity was evaluated with the I2 statistic. Results: Eighteen eligible studies (n=7766 participants) reported PASS from pain PROMs in people with knee pain. All studies were longitudinal and observational, undertaken within the context of a treatment for knee pain. Identified PROMS were the Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Numerical Rating Scale (NRS) and the Visual Analogue Scale (VAS). Most studies were of low risk of bias (8/18), with 6/18 of moderate and 4/18 of high risk of bias. Thirteen studies (n=6339 participants) reported data that allowed their inclusion in metaanalysis models. The pooled pain PASS score was 27 (95%CI: 21 to 35; n=6339 participants) with significant heterogeneity (I2 =96%, p <0.01) (Figure). No significant differences (Q=2.07, p = 0.36) were observed between PASS scores derived for the different knee pain PROMs (KOOS: 23, 95%CI: 16 to 30; WOMAC: 28, 95% CI: 23 to 32; NRS or VAS: 35, 95%CI: 24 to 45). Lower estimates of PASS were associated with lower baseline pain (β=0.60, p=0.02), longer time to follow up at which PASS was estimated (6-months 30, 95%CI: 20 to 40; 12-months: 24, 95%CI: 17 to 30; more than 12-months: 16, 95% CI: 9 to 22), and with surgical (24, 95%CI: 17 to 30) rather than non-surgical interventions (40, 95%CI: 29 to 52). PASS scores were similar between knee osteoarthritis (31, 95%CI: 26 to 36) and meniscal tear (27, 95%CI: 20 to 35) but lower for ligament tears (12, 95%CI: 11 to 13). Observed differences in estimates of PASS due to risk of bias (low: 23, 95%CI: 11 to 35; moderate: 34, 95%CI: 24 to 45; high: 26, 95%CI: 21 to 31) were not significant (Q=1.93, p = 0.38).Conclusions: Standardised knee pain PROMs scores of approximately 30/100 are considered acceptable by people with knee pain. The level of pain that is acceptable might depend upon the baseline pain severity (higher with worse baseline pain), decrease with time from commencing an intervention and vary according to diagnostic or treatment group. However, different knee pain PROMs when transformed produce similar PASS scores, suggesting that standardised scores derived from multiple instruments might be validly combined in large multicentre studies using historically collected data

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure

Background: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. / Methods: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. / Results: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). / Conclusions: Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid

Background: Observational studies showed that circulating L-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. Objectives: We assessed the relation between L-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating L-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-L-ascorbic acid and L-ascorbic acid-outcome associations. Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between L-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (-0.13-SD change; 95% CI: -0.20-, -0.07-SD change; P = 0.0001) per SD increase in L-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10⁻⁶) increase in L-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected.The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of L-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between L-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.Kaitlin H Wade, Nita G Forouhi, Derek G Cook, Paul Johnson, Alex McConnachie, Richard W Morris, Santiago Rodriguez, Zheng Ye, Shah Ebrahim, Sandosh Padmanabhan, Graham Watt, K Richard Bruckdorfer, Nick J Wareham, Peter H Whincup, Stephen Chanock, Naveed Sattar, Debbie A Lawlor, George Davey Smith and Nicholas J Timpso

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK