On Inflation with Non-minimal Coupling

A simple realization of inflation consists of adding the following operators to the Einstein-Hilbert action: (partial phi)^2, lambda phi^4, and xi phi^2 R, with xi a large non-minimal coupling. Recently there has been much discussion as to whether such theories make sense quantum mechanically and if the inflaton phi can also be the Standard Model Higgs. In this note we answer these questions. Firstly, for a single scalar phi, we show that the quantum field theory is well behaved in the pure gravity and kinetic sectors, since the quantum generated corrections are small. However, the theory likely breaks down at ~ m_pl / xi due to scattering provided by the self-interacting potential lambda phi^4. Secondly, we show that the theory changes for multiple scalars phi with non-minimal coupling xi phi dot phi R, since this introduces qualitatively new interactions which manifestly generate large quantum corrections even in the gravity and kinetic sectors, spoiling the theory for energies > m_pl / xi. Since the Higgs doublet of the Standard Model includes the Higgs boson and 3 Goldstone bosons, it falls into the latter category and therefore its validity is manifestly spoiled. We show that these conclusions hold in both the Jordan and Einstein frames and describe an intuitive analogy in the form of the pion Lagrangian. We also examine the recent claim that curvature-squared inflation models fail quantum mechanically. Our work appears to go beyond the recent discussions.Comment: 14 pages, 2 figures. Version 2: Clarified findings and improved wording. Elaborated important sections and removed an unnecessary section. Added references. Version 3: Updated towards JHEP version. Version 4: Final JHEP versio

Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)

Travel to school and housing markets: a case study of Sheffield, England

How children travel to school is at the centre of a complex set of interrelated issues with significant policy implications. This paper reviews the relation of patterns of travel to school to concerns about public health, school choice, urban form, and residential housing markets. The spatial relations between pupils’ homes and the schools that they attend provides the basis of an analytical framework that links local neighbourhood characteristics, school performance, and house prices to the distance and mode of travel to school and the level of ‘excess commuting’ in the urban system. A unique analysis of several integrated micro-datasets from Sheffield, UK, suggests that, while there are high levels of excess commuting, there remains a complex interrelationship between housing and neighbourhood characteristics, school performance, and commuting patterns. There are differences between the pictures for primary schools and secondary schools. Policies aimed at promoting transport efficiency and those promoting school choice are likely to remain in tension

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

Comparing online campaigning: The evolution of interactive campaigning from Royal to Obama to Hollande

© 2016 Macmillan Publishers Ltd.Studies of election campaigning from a comparative perspective have a long history; this study approaches the topic through a most-similar regime perspective to explore the ebb and flow of innovations in digital campaigning between presidential campaigns in France and the United States. The hype surrounding the 2008 Obama campaign overshadowed innovations in France the previous year, while the 2011 contest gained little serious academic attention. Using a well-established content analysis methodology the research explains the strategic design of the digital dimension of the campaigns of the leading candidates (Sarkozy and Royal in 2007, Obama and McCain in 2008, Hollande and Sarkozy in 2011, and Obama and Romney in 2012). The research then assesses the strategic contribution of each feature using schematics for understanding the flow of communication, as well as the strategy employed by each candidate. The key findings are that the campaigns are becoming more interactive, with the citizens increasingly more able to enter into conversations with the campaign teams, however interactivity when it happens is carefully controlled. Largely, however, there is a strong similarity masked by the sophistication of US contests. Despite the advances in communication technology and the social trends they have instigated, campaign communication remains top-down and digital technologies are used to gather data and push supporters towards activism than creating an inclusive space for the co-creation that cyberoptimists argued would revitalise the structures of democracy

Studying the Salt Dependence of the Binding of σ70 and σ32 to Core RNA Polymerase Using Luminescence Resonance Energy Transfer

The study of protein-protein interactions is becoming increasingly important for understanding the regulation of many cellular processes. The ability to quantify the strength with which two binding partners interact is desirable but the accurate determination of equilibrium binding constants is a difficult process. The use of Luminescence Resonance Energy Transfer (LRET) provides a homogeneous binding assay that can be used for the detection of protein-protein interactions. Previously, we developed an LRET assay to screen for small molecule inhibitors of the interaction of σ70 with theβ' coiled-coil fragment (amino acids 100–309). Here we describe an LRET binding assay used to monitor the interaction of E. coli σ70 and σ32 with core RNA polymerase along with the controls to verify the system. This approach generates fluorescently labeled proteins through the random labeling of lysine residues which enables the use of the LRET assay for proteins for which the creation of single cysteine mutants is not feasible. With the LRET binding assay, we are able to show that the interaction of σ70 with core RNAP is much more sensitive to NaCl than to potassium glutamate (KGlu), whereas the σ32 interaction with core RNAP is insensitive to both salts even at concentrations >500 mM. We also find that the interaction of σ32 with core RNAP is stronger than σ70 with core RNAP, under all conditions tested. This work establishes a consistent set of conditions for the comparison of the binding affinities of the E.coli sigma factors with core RNA polymerase. The examination of the importance of salt conditions in the binding of these proteins could have implications in both in vitro assay conditions and in vivo function

Women's knowledge and beliefs regarding breast cancer

Approximately 20–30% of women delay for 12 weeks or more from self-discovery of a breast symptom to presentation to a health care provider, and such delay intervals are associated with poorer survival. Understanding the factors that influence patient delay is important for the development of an effective, targeted health intervention programme to shorten patient delay. The aim of the study was to elicit knowledge and beliefs about breast cancer among a sample of the general female population, and examine age and socio-economic variations in responses. Participants were randomly selected through the Postal Address File, and data were collected through the Office of National Statistics. Geographically distributed throughout the UK, 996 women participated in a short structured interview to elicit their knowledge of breast cancer risk, breast cancer symptoms, and their perceptions of the management and outcomes associated with breast cancer. Women had limited knowledge of their relative risk of developing breast cancer, of associated risk factors and of the diversity of potential breast cancer-related symptoms. Older women were particularly poor at identifying symptoms of breast cancer, risk factors associated with breast cancer and their personal risk of developing the disease. Poorer knowledge of symptoms and risks among older women may help to explain the strong association between older age and delay in help-seeking. If these findings are confirmed they suggest that any intervention programme should target older women in particular, given that advancing age is a risk factor for both developing breast cancer and for subsequent delayed presentation

Injectable Poly-l-Lactic Acid: A Novel Sculpting Agent for the Treatment of Dermal Fat Atrophy After Severe Acne

Acne vulgaris affects up to 80% of people 11 to 30 years of age, and scarring can occur for up to 95% of these patients. Scarring may be pitted or hypertrophic in nature, although in most cases it is atrophic. Atrophic acne scarring follows dermal collagen and fat loss after moderate to severe acne infection. Injectable poly-L-acid (PLLA) is a biocompatible, biodegradable, synthetic polymer device that is hypothesized to enhance dermal volume via the endogenous production of fibroblasts and, subsequently, collagen. The gradual improvements in cutaneous volume observed after treatment with injectable PLLA have been noted to last up to 2 years. The case studies presented describe the use of injectable PLLA to correct dermal fat loss in macular atrophic acne scarring of the cheeks. Two female patients underwent three treatment sessions with injectable PLLA over a 12-week period. At each treatment session, the reconstituted product was injected into the deep dermis under the depressed portion of the scar. Both patients were extremely pleased with their results at, respectively, 1- and 4-year follow-up evaluations. Patients experienced minimal swelling and redness after injection and no product-related adverse events such as papule and/or nodule formation. The author believes these data suggest that injectable PLLA is a good treatment option for the correction of macular atropic scarring with thin dermis (off-label use), particularly compared with other injectable fillers currently used for this indication that have shorter durations of effect

Stereotyping of medical disability claimants' communication behaviour by physicians: towards more focused education for social insurance physicians

Background: Physicians who hold medical disability assessment interviews (social insurance physicians) are probably influenced by stereotypes of claimants, especially because they have limited time available and they have to make complicated decisions. Because little is known about the influences of stereotyping on assessment interviews, the objectives of this paper were to qualitatively investigate: (1) the content of stereotypes used to classify claimants with regard to the way in which they communicate; (2) the origins of such stereotypes; (3) the advantages and disadvantages of stereotyping in assessment interviews; and (4) how social insurance physicians minimise the undesirable influences of negative stereotyping. Methods: Data were collected during three focus group meetings with social insurance physicians who hold medical disability assessment interviews with sick-listed employees (i.e. claimants). The participants also completed a questionnaire about demographic characteristics. The data were qualitatively analysed in Atlas.ti in four steps, according to the grounded theory and the principle of constant comparison. Results: A total of 22 social insurance physicians participated. Based on their responses, a claimant's communication was classified with regard to the degree of respect and acceptance in the physician-claimant relationship, and the degree of dominance. Most of the social insurance physicians reported that they classify claimants in general groups, and use these classifications to adapt their own communication behaviour. Moreover, the social insurance physicians revealed that their stereotypes originate from information in the claimants' files and first impressions. The main advantages of stereotyping were that this provides a framework for the assessment interview, it can save time, and it is interesting to check whether the stereotype is correct. Disadvantages of stereotyping were that the stereotypes often prove incorrect, they do not give the complete picture, and the claimant's behaviour changes constantly. Social insurance physicians try to minimise the undesirable influences of stereotypes by being aware of counter transference, making formal assessments, staying neutral to the best of their ability, and being compassionate. Conclusions: We concluded that social insurance physicians adapt their communication style to the degree of respect and dominance of claimants in the physician-claimant relationship, but they try to minimise the undesirable influences of stereotypes in assessment interviews. It is recommended that this issue should be addressed in communication skills trainin

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

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