Failure of the Mycobacterium bovis BCG vaccine: Some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis

The efficacy of Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG vaccination and controls the multiplication of the vaccine. In these sensitized mice, BCG elicits only a transient immune response with a low frequency of mycobacterium-specific cells and no protective immunity against TB. In contrast, the efficacy of TB subunit vaccines was unaffected by prior exposure to environmental mycobacteria. Six different isolates from soil and sputum samples from Karonga district in Northern Malawi (a region in which BCG vaccination has no effect against pulmonary TB) were investigated in the mouse model, and two strains of the Mycobacterium avium complex were found to block BCG activity completely

Discrete sine transform for multi-scale realized volatility measures

In this study we present a new realized volatility estimator based on a combination of the multi-scale regression and discrete sine transform (DST) approaches. Multi-scale estimators similar to that recently proposed by Zhang (2006) can, in fact, be constructed within a simple regression-based approach by exploiting the linear relation existing between the market microstructure bias and the realized volatilities computed at different frequencies. We show how such a powerful multi-scale regression approach can also be applied in the context of the Zhou [Nonlinear Modelling of High Frequency Financial Time Series, pp. 109–123, 1998] or DST orthogonalization of the observed tick-by-tick returns. Providing a natural orthonormal basis decomposition of observed returns, the DST permits the optimal disentanglement of the volatility signal of the underlying price process from the market microstructure noise. The robustness of the DST approach with respect to the more general dependent structure of the microstructure noise is also shown analytically. The combination of the multi-scale regression approach with DST gives a multi-scale DST realized volatility estimator similar in efficiency to the optimal Cramer–Rao bounds and robust against a wide class of noise contamination and model misspecification. Monte Carlo simulations based on realistic models for price dynamics and market microstructure effects show the superiority of DST estimators over alternative volatility proxies for a wide range of noise-to-signal ratios and different types of noise contamination. Empirical analysis based on six years of tick-by-tick data for the S&P 500 index future, FIB 30, and 30 year U.S. Treasury Bond future confirms the accuracy and robustness of DST estimators for different types of real data

Accurate masses and radii of normal stars: modern results and applications

This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl

Non-Perturbative Renormalization Group for Simple Fluids

We present a new non perturbative renormalization group for classical simple fluids. The theory is built in the Grand Canonical ensemble and in the framework of two equivalent scalar field theories as well. The exact mapping between the three renormalization flows is established rigorously. In the Grand Canonical ensemble the theory may be seen as an extension of the Hierarchical Reference Theory (L. Reatto and A. Parola, \textit{Adv. Phys.}, \textbf{44}, 211 (1995)) but however does not suffer from its shortcomings at subcritical temperatures. In the framework of a new canonical field theory of liquid state developed in that aim our construction identifies with the effective average action approach developed recently (J. Berges, N. Tetradis, and C. Wetterich, \textit{Phys. Rep.}, \textbf{363} (2002))

Acceptability of novel lifelogging technology to determine context of sedentary behaviour in older adults

<strong>Objective:</strong> Lifelogging, using body worn sensors (activity monitors and time lapse photography) has the potential to shed light on the context of sedentary behaviour. The objectives of this study were to examine the acceptability, to older adults, of using lifelogging technology and indicate its usefulness for understanding behaviour.<strong> </strong><strong>Method:</strong> 6 older adults (4 males, mean age: 68yrs) wore the equipment (ActivPAL^TM and Vicon Revue^TM/SenseCam^TM) for 7 consecutive days during free-living activity. The older adults’ perception of the lifelogging technology was assessed through semi-structured interviews, including a brief questionnaire (Likert scale), and reference to the researcher&#39;s diary. <strong>Results:</strong> Older adults in this study found the equipment acceptable to wear and it did not interfere with privacy, safety or create reactivity, but they reported problems with the actual technical functioning of the camera. <strong>Conclusion:</strong> This combination of sensors has good potential to provide lifelogging information on the context of sedentary behaviour

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics\ud

Objective: To investigate the impact of upper extremity deficit in subjects with tetraplegia.\ud \ud Setting: The United Kingdom and The Netherlands.\ud \ud Study design: Survey among the members of the Dutch and UK Spinal Cord Injury (SCI) Associations.\ud \ud Main outcome parameter: Indication of expected improvement in quality of life (QOL) on a 5-point scale in relation to improvement in hand function and seven other SCI-related impairments.\ud \ud Results: In all, 565 subjects with tetraplegia returned the questionnaire (overall response of 42%). Results in the Dutch and the UK group were comparable. A total of 77% of the tetraplegics expected an important or very important improvement in QOL if their hand function improved. This is comparable to their expectations with regard to improvement in bladder and bowel function. All other items were scored lower.\ud \ud Conclusion: This is the first study in which the impact of upper extremity impairment has been assessed in a large sample of tetraplegic subjects and compared to other SCI-related impairments that have a major impact on the life of subjects with SCI. The present study indicates a high impact as well as a high priority for improvement in hand function in tetraplegics.\ud \u

Cohort profile: Design and implementation of the Danish Physiotherapy Research Database for patients receiving primary care with chronic disease

PurposeFree of charge physiotherapy (FCP) is free physiotherapy provided by the Danish government for patients with a range of chronic diseases. To date, the population has not been described in depth making evaluation and decision making difficult. The purpose of this study was to (1) describe the development and the content of a novel clinical physiotherapy database for FCP (PhysDB-FCP) and (2) present the cohort profile based on the data collected.ParticipantsNinety-nine clinics (17 460 FCP patients) were invited to participate in the development process from 2018 to 2019. Eleven clinics consented (2780 FCP patients) and 534 patients performed the physiotherapy assessment using the PhysDB-FCP tool, with 393/534 completing the patient survey.Findings to dateThe content of the PhysDB-FCP was developed through an iterative process involving consensus between clinical and research workgroups. Prior to using the tool all consenting sites received training to use/administer the tool. All data were collected/stored using the PhysDB-FCP. Items finally chosen for the PhysDB-FCP included demographic information, questions about health status and daily functioning, functional tests, treatment plan and validated questionnaires. The initial patient cohort composed of 63.4% women with main diagnoses of multiple sclerosis (22.7%) and Parkinson’s disease (17.0%). The ability to perform personal/instrumental activities of daily living and functional ability varied widely. Other non-physiotherapy related issues were identified in numerous patients (ie, 34.9% of patients were at risk of depression) and multidisciplinary interventional approaches could be considered.Future plansThe current study has provided a comprehensive description of patients receiving FCP, using data collected from the novel PhysDB-FCP. Collected information can be used to facilitate microlevel to macrolevel programme evaluation and decisions. Although the PhysDB-FCP is promising, the tool requires optimisation before it is implemented regionally and/or nationally.</jats:sec

Defining antimicrobial prescribing quality indicators: what is a new prescription?

Contains fulltext : 95791.pdf (publisher's version ) (Open Access): Since guidelines on antibiotic drug treatment often focus on appropriate first choice drugs, assessment of guideline adherence should only concentrate on the first drug prescribed, and not on subsequent antibiotics prescribed after failure of the first one. PURPOSE: To determine a valid cut-off point for a definition of "first" or "new" prescription in indicators for the assessment of the quality of antibiotic drug treatment on the basis of pharmaceutical data. METHODS: Three possible definitions for the term "new prescription" were compared, based on three different periods of time, viz. more than 35, 28, or 21 days after starting a previous antibiotic. In an observational study, 1,225 antimicrobial prescriptions from the medical files of five family practices were audited ("clinical classification") and compared with a classification based on the three definitions ("technical classification"). Agreement between these clinical and technical classifications was determined by calculating Cohen's kappa. The technical classification was analyzed as a diagnostic test, using the clinical classification as the gold standard, and sensitivity, specificity, likelihood ratios, and post-test probabilities were calculated. RESULTS: Defining "new prescription" as "more than 35 days after a previous prescription was issued" resulted in a Cohen's kappa of 0.93 (95% CI 0.92-0.98). The diagnostic value of this definition was extremely high, with a sensitivity of 0.976, specificity of 0.987, positive likelihood ratio of 77.7, and negative likelihood ratio of 0.02. CONCLUSION: We recommend using a cut-off value of 35 days since the last antimicrobial prescription as the definition of a "new prescription" when no diagnostic information is available, i.e., when using pharmaceutical data to assess the quality of antibiotic prescribing behavior.01 januari 201