Gauge symmetry and W-algebra in higher derivative systems

The problem of gauge symmetry in higher derivative Lagrangian systems is discussed from a Hamiltonian point of view. The number of independent gauge parameters is shown to be in general {\it{less}} than the number of independent primary first class constraints, thereby distinguishing it from conventional first order systems. Different models have been considered as illustrative examples. In particular we show a direct connection between the gauge symmetry and the W-algebra for the rigid relativistic particle.Comment: 1+22 pages, 1 figure, LaTeX, v2; title changed, considerably expanded version with new results, to appear in JHE

Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application

Background The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). Results The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection. Conclusions E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

A discrete choice experiment to explore patients’ willingness to risk disease relapse from treatment withdrawal in psoriatic arthritis

The objective of this study is to assess patient preferences for treatment-related benefits and risk of disease relapse in the management of low disease states of psoriatic arthritis (PsA). Focus groups with patients and a literature review were undertaken to determine the characteristics of treatment and symptoms of PsA important to patients. Patient preferences were assessed using a discrete choice experiment which compared hypothetical treatment profiles of the risk and benefits of treatment withdrawal. The risk outcome included increased risk of disease relapse, while benefit outcomes included reduced sickness/nausea from medication and changes in health-related quality of life. Each patient completed 12 choice sets comparing treatment profiles. Preference weights were estimated using a logic regression model, and the maximum acceptable risk in disease relapse for a given improvement in benefit outcomes was elicited. Final sample included 136 patients. Respondents attached the greatest importance to eliminating severe side effects of sickness/nausea and the least importance to a change in risk of relapse. Respondents were willing to accept an increase in the risk of relapse of 32.6 % in order to eliminate the side effects of sickness/nausea. For improvements in health status, the maximum acceptable risk in relapse was comparable to a movement from some to no sickness/nausea. The study suggests that patients in low disease states of PsA are willing to accept greater risks of relapse for improvements in side effects of sickness/nausea and overall health status, with the most important benefit attribute being the elimination of severe sickness or nausea

The Proprioceptive Map of the Arm Is Systematic and Stable, but Idiosyncratic

Visual and somatosensory signals participate together in providing an estimate of the hand's spatial location. While the ability of subjects to identify the spatial location of their hand based on visual and proprioceptive signals has previously been characterized, relatively few studies have examined in detail the spatial structure of the proprioceptive map of the arm. Here, we reconstructed and analyzed the spatial structure of the estimation errors that resulted when subjects reported the location of their unseen hand across a 2D horizontal workspace. Hand position estimation was mapped under four conditions: with and without tactile feedback, and with the right and left hands. In the task, we moved each subject's hand to one of 100 targets in the workspace while their eyes were closed. Then, we either a) applied tactile stimulation to the fingertip by allowing the index finger to touch the target or b) as a control, hovered the fingertip 2 cm above the target. After returning the hand to a neutral position, subjects opened their eyes to verbally report where their fingertip had been. We measured and analyzed both the direction and magnitude of the resulting estimation errors. Tactile feedback reduced the magnitude of these estimation errors, but did not change their overall structure. In addition, the spatial structure of these errors was idiosyncratic: each subject had a unique pattern of errors that was stable between hands and over time. Finally, we found that at the population level the magnitude of the estimation errors had a characteristic distribution over the workspace: errors were smallest closer to the body. The stability of estimation errors across conditions and time suggests the brain constructs a proprioceptive map that is reliable, even if it is not necessarily accurate. The idiosyncrasy across subjects emphasizes that each individual constructs a map that is unique to their own experiences

Early intervention for adolescents with Patellofemoral Pain Syndrome - a pragmatic cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Self-reported knee pain is highly prevalent among adolescents. As much as 50% of the non-specific knee pain may be attributed to Patellofemoral Pain Syndrome (PFPS). In the short term, exercise therapy appears to have a better effect than patient education consisting of written information and general advice on exercise or compared with placebo treatment. But the long-term effect of exercise therapy compared with patient education is conflicting. The purpose of this study is to examine the short- and long-term effectiveness of patient education compared with patient education and multimodal physiotherapy applied at a very early stage of the condition among adolescents.</p> <p>Methods/Design</p> <p>This study is a single blind pragmatic cluster randomised controlled trial. Four upper secondary schools have been invited to participate in the study (approximately 2500 students, aged 15-19 years). Students are asked to answer an online questionnaire regarding musculoskeletal pain. The students who report knee pain are contacted by telephone and offered a clinical examination by a rheumatologist. Subjects who fit the inclusion criteria and are diagnosed with PFPS are invited to participate in the study. A minimum of 102 students with PFPS are then cluster-randomised into two intervention groups based on which school they attend. Both intervention groups receive written information and education. In addition to patient education, one group receives multimodal physiotherapy consisting primarily of neuromuscular training of the muscles around the foot, knee and hip and home exercises.</p> <p>The students with PFPS fill out self-reported questionnaires at baseline, 3, 6, 12 and 24 months after inclusion in the study. The primary outcome measure is perception of recovery measured on a 7-point Likert scale ranging from "completely recovered" to "worse than ever" at 12 months.</p> <p>Discussion</p> <p>This study is designed to investigate the effectiveness of patient education compared with patient education combined with multimodal physiotherapy. If patient education and multimodal physiotherapy applied at an early stage of Patellofemoral Pain Syndrome proves effective, it may serve as a basis for optimising the clinical pathway for those suffering from the condition, where specific emphasis can be placed on early diagnosis and early treatment.</p> <p>Trial Registration</p> <p>clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438762">NCT01438762</a></p

Illness cognitions in head and neck squamous cell carcinoma: predicting quality of life outcome

Goals of work: This paper presents an observational study of the longitudinal effects of cancer treatment on quality of life (QoL) in patients treated for head and neck squamous cell carcinoma (HNSCC), and evaluated the contribution of patients' baseline illness cognitions to the prediction of QoL 2 years after diagnosis. Patients and methods: One hundred seventy-seven patients eligible for primary treatment for HNSCC completed the Illness Perception Questionnaire-Revised at baseline and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-30 at baseline, at 1-year and 2-year follow-ups. Main results Compared to baseline, patients reported better emotional functioning at both follow-ups (p<0.001), worse social functioning at 12 months (p<0.05), and better global health

Different Temporal Structure for Form versus Surface Cortical Color Systems – Evidence from Chromatic Non-Linear VEP

Physiological studies of color processing have typically measured responses to spatially varying chromatic stimuli such as gratings, while psychophysical studies of color include color naming, color and light, as well as spatial and temporal chromatic sensitivities. This raises the question of whether we have one or several cortical color processing systems. Here we show from non-linear analysis of human visual evoked potentials (VEP) the presence of distinct and independent temporal signatures for form and surface color processing. Surface color stimuli produced most power in the second order Wiener kernel, indicative of a slowly recovering neural system, while chromatic form stimulation produced most power in the first order kernel (showing rapid recovery). We find end-spectral saturation-dependent signals, easily separable from achromatic signals for surface color stimuli. However physiological responses to form color stimuli, though varying somewhat with saturation, showed similar waveform components. Lastly, the spectral dependence of surface and form color VEP was different, with the surface color responses almost vanishing with yellow-grey isoluminant stimulation whereas the form color VEP shows robust recordable signals across all hues. Thus, surface and form colored stimuli engage different neural systems within cortex, pointing to the need to establish their relative contributions under the diverse chromatic stimulus conditions used in the literature

Where’s WALY? : A proof of concept study of the ‘wellbeing adjusted life year’ using secondary analysis of cross-sectional survey data

Background The Quality-Adjusted Life Year (QALY) is a measure that combines life extension and health improvement in a single score, reflecting preferences around different types of health gain. It can therefore be used to inform decision-making around allocation of health care resources to mutually exclusive options that would produce qualitatively different health benefits. A number of quality-of-life instruments can be used to calculate QALYs. The EQ-5D is one of the most commonly used, and is the preferred option for submissions to NICE (https://www.nice.org.uk/process/pmg9/). However, it has limitations that might make it unsuitable for use in areas such as public and mental health where interventions may aim to improve well-being. One alternative to the QALY is a Wellbeing-Adjusted Life Year. In this study we explore the need for a Wellbeing-Adjusted Life Year measure by examining the extent to which a measure of wellbeing (the Warwick-Edinburgh Mental Well-being Scale) maps onto the EQ-5D-3L. Methods Secondary analyses were conducted on data from the Coventry Household Survey in which 7469 participants completed the EQ-5D-3L, Warwick-Edinburgh Mental Well-being Scale, and a measure of self-rated health. Data were analysed using descriptive statistics, Pearson’s and Spearman’s correlations, linear regression, and receiver operating characteristic curves. Results Approximately 75 % of participants scored the maximum on the EQ-5D-3L. Those with maximum EQ-5D-3L scores reported a wide range of levels of mental wellbeing. Both the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were able to detect differences between those with higher and lower levels of self-reported health. Linear regression indicated that scores on the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were weakly, positively correlated (with R2 being 0.104 for the index and 0.141 for the visual analogue scale). Conclusion The Warwick-Edinburgh Mental Well-being Scale maps onto the EQ-5D-3L to only a limited extent. Levels of mental wellbeing varied greatly amongst participants who had the maximum score on the EQ-5D-3L. To evaluate the relative effectiveness of interventions that impact on mental wellbeing, a new measure – a Wellbeing Adjusted Life Year – is needed

Predicting general and cancer-related distress in women with newly diagnosed breast cancer

Background: Psychological distress can impact medical outcomes such as recovery from surgery and experience of side effects during treatment. Identifying the factors that explain variability in distress would guide future interventions aimed at decreasing distress. Two factors that have been implicated in distress are illness perceptions and coping, and are part of the Self-Regulatory Model of Illness Behaviour (SRM). The model suggests that coping mediates the relationship between illness perceptions and distress. Despite this; very little research has assessed this relationship with cancer-related distress, and none have examined women with screen-detected breast cancer. This study is the first to examine the relative contribution of illness perceptions and coping on general and cancer-related distress in women with screen-detected breast cancer. Methods: Women recently diagnosed with breast cancer (N = 94) who had yet to receive treatment completed measures of illness perceptions (Revised Illness Perception Questionnaire), cancer-specific coping (Mental Adjustment to Cancer Scale), general anxiety and depression (Hospital Anxiety and Depression scale), and cancer-related distress. Results: Hierarchical regression analyses revealed that medical variables, illness perceptions and coping predicted 50% of the variance in depression, 42% in general anxiety, and 40% in cancer-related distress. Believing in more emotional causes to breast cancer (beta = .22, p = .021), more illness identity (beta = .25, p = .004), greater anxious preoccupation (beta = .23, p = .030), and less fighting spirit (beta = -.31, p = .001) predicted greater depression. Greater illness coherence predicted less cancer-related distress (beta = -.20, p = .043). Greater anxious preoccupation also led to greater general anxiety (beta = .44, p &amp;lt; .001) and cancer-related distress (beta = .37, p = .001). Mediation analyses revealed that holding greater beliefs in a chronic timeline, more severe consequences, greater illness identity and less illness coherence increases cancer-specific distress (ps &amp;lt; .001) only if women were also more anxiously preoccupied with their diagnosis. Conclusions: Screening women for anxious preoccupation may help identify women with screen-detected breast cancer at risk of experiencing high levels of cancer-related distress; whilst illness perceptions and coping could be targeted for use in future interventions to reduce distress