Symmetry implies independence

Given a quantum system consisting of many parts, we show that symmetry of the system's state, i.e., invariance under swappings of the subsystems, implies that almost all of its parts are virtually identical and independent of each other. This result generalises de Finetti's classical representation theorem for infinitely exchangeable sequences of random variables as well as its quantum-mechanical analogue. It has applications in various areas of physics as well as information theory and cryptography. For example, in experimental physics, one typically collects data by running a certain experiment many times, assuming that the individual runs are mutually independent. Our result can be used to justify this assumption.Comment: LaTeX, contains 4 figure

Dispositional disinhibition and alcohol use disorders: personality, risk appraisal and problematic alcohol consumption

Background: The relationship between psychopathic personality and problematic alcohol consumption could be important for understanding risk and potential interventions. This existing work on psychopathy and alcohol abuse is typically conducted in criminal and hospitalised populations and little attention has been paid to investigating the general populations’ psychopathic personality and problematic consumption of alcohol. The psychopathy-focused Triarchic Psychopathy Measure (TriPM) and the more general Reinforcement Sensitivity Theory of personality (RST) focus on individual differences related to low self-control and sensation seeking, and could relate to problematic alcohol consumption in non-forensic samples. The current study brings together RST and psychopathic personality traits to predict alcohol use disorders. We hypothesise that impulsivity and anxiety predict problematic alcohol consumption and related risk appraisal. Methods: We analysed data from a sample of 349 general population participants who had completed measures of the TriPM, RST, alcohol use disorders (AUDIT) and their perceived negative outcomes of high risk behaviour with the Cognitive Appraisal of Risky Events (CARE) measure. Results: We find some evidence that TriPM’s disinhibition and RST’s anxious personality traits relate to AUDIT scores. We find limited evidence that personality traits predict the negative appraisal of risky events, but alcohol use was related to increased perceptions of the negative outcomes of alcohol consumption. Conclusions: Overall this study shows that individual differences do relate to problematic alcohol consumption but not the appraisal of risks related to alcohol consumption. This has implications for the structuring of intervention for those at risk of problematic consumption of alcohol

Identification of type III secretion inhibitors for plant disease management

Bacterial plant pathogens are among the most devastating threats to agriculture. To date, there are no effective means to control bacterial plant diseases due to the restrictions in the use of antibiotics in agriculture. A novel strategy under study is the use of chemical compounds that inhibit the expression of key bacterial virulence determinants. The type III secretion system is essential for virulence of many Gram-negative bacteria because it injects into the plant host cells bacterial proteins that interfere with their immune system. Here, we describe the methodology to identify bacterial type III secretion inhibitors, including a series of protocols that combine in planta and in vitro experiments. We use Ralstonia solanacearum as a model because of the number of genetic tools available in this organism and because it causes bacterial wilt, one of the most threatening plant diseases worldwide. The procedures presented can be used to evaluate the effect of different chemical compounds on bacterial growth and virulence

Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

This is the final published version. Available from PLoS via the DOI in this record.All relevant data are available from Figshare, under the DOI http://dx.doi. org/10.6084/m9.figshare.1292883.AIMS: Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. MATERIALS AND METHODS: The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2)) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. RESULTS: Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). CONCLUSIONS: Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.Diabetes Research and Wellness FoundatioMedical Research Council (MRC)Astra Zenec

Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo

Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1-40 microM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (>/=5 microM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w(-1)) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 microM and 0.11 and 63 nmol g(-1), respectively. Cells were exposed to tricin (0.11, 1.1 or 11 microM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 microM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 microM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

A report from the NIHR UK working group on remote trial delivery for the COVID-19 pandemic and beyond

Abstract Background Prior to the COVID-19 pandemic, the majority of clinical trial activity took place face to face within clinical or research units. The COVID-19 pandemic resulted in a significant shift towards trial delivery without in-person face-to-face contact or “Remote Trial Delivery”. The National Institute of Health Research (NIHR) assembled a Remote Trial Delivery Working Group to consider challenges and enablers to this major change in clinical trial delivery and to provide a toolkit for researchers to support the transition to remote delivery. Methods The NIHR Remote Trial Delivery Working Group evaluated five key domains of the trial delivery pathway: participant factors, recruitment, intervention delivery, outcome measurement and quality assurance. Independent surveys were disseminated to research professionals, and patients and carers, to ascertain benefits, challenges, pitfalls, enablers and examples of good practice in Remote Trial Delivery. A toolkit was constructed to support researchers, funders and governance structures in moving towards Remote Trial Delivery. The toolkit comprises a website encompassing the key principles of Remote Trial Delivery, and a repository of best practice examples and questions to guide research teams. Results The patient and carer survey received 47 respondents, 34 of whom were patients and 13 of whom were carers. The professional survey had 115 examples of remote trial delivery practice entered from across England. Key potential benefits included broader reach and inclusivity, the ability for standardisation and centralisation, and increased efficiency and patient/carer convenience. Challenges included the potential exclusion of participants lacking connectivity or digital skills, the lack of digitally skilled workforce and appropriate infrastructure, and validation requirements. Five key principles of Remote Trial Delivery were proposed: national research standards, inclusivity, validity, cost-effectiveness and evaluation of new methodologies. Conclusions The rapid changes towards Remote Trial Delivery catalysed by the COVID-19 pandemic could lead to sustained change in clinical trial delivery. The NIHR Remote Trial Delivery Working Group provide a toolkit for researchers recommending five key principles of Remote Trial Delivery and providing examples of enablers. </jats:sec

Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level

A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis

Purpose: The purpose of this study is to elicit the role of oral low-dose sirolimus as a corticosteriod-sparing agent for active uveitis. Methods: A retrospective, interventional case series was performed by reviewing the clinical records of all patients treated with oral, low-dose sirolimus (1-4 mg daily) for severe uveitis. Data reviewed included symptomatic improvement, Snellen best-corrected visual acuity, corticosteroid requirement, sirolimus levels, intraocular inflammation, spectral-domain optical coherence tomography, and fluorescein angiogram. Primary outcome measures were determined by the ability to decrease the intraocular inflammation, corticosteroid requirement, and frequency of flares. Results: Eight patients with varied diagnoses were treated with oral low-dose sirolimus for severe, chronic uveitis between 2008 and 2010. In four of the eight patients, there was an improvement of all primary outcome measures. While sirolimus monotherapy was successful in only one patient, a sirolimus/methotrexate combination was successful in three patients. Although there was a good initial response in three patients, treatment was a failure after serious side effects forced the cessation of sirolimus therapy. One patient was lost to follow-up. Conclusion: Sirolimus may have a limited role in severe uveitis as an adjunct corticosteroid-sparing agent in combination with more standard immunosuppressive agents. Oral low-dose sirolimus appeared to be better tolerated than higher doses, but there were a significant number of adverse events, requiring therapy to be stopped. © 2010 The Author(s)