Emerging drugs for Cushing's disease

INTRODUCTION: Considering the effects of uncontrolled hypercortisolism on morbidity and mortality, there is a clear need for effective medical therapy for patients with Cushing's disease (CD). Therefore, the search for new medical effective tools remains active, and already promising results have been obtained. AREAS COVERED: The importance of the design and conduct of trials to validate old drugs or to test new compounds is discussed. The results of the ongoing clinical trials, targeting the specific properties of drugs, such as ketoconazole, LCI699, mifepristone, etomidate and pasireotide, are also reported. The authors also emphasise the advantages and drawbacks of each particular drug, and the potential combined use of agents with complementary mechanisms of action. EXPERT OPINION: CD is an excellent example of a situation where effective therapy is essential, but where the balance of risk and benefit must be carefully judged. Metyrapone is the drug of choice when rapid control of the hypercortisolaemia is required, ketoconazole represents a good second-line drug, although in the future LCI699 may be a better alternative. Mifepristone can also be used in the rare situation when previous drugs are inappropriate. Etomidate is useful where immediate parenteral action is required. For drugs working directly on the pituitary, cabergoline is occasionally effective and pasireotide can be attempted in patients with mild CD.info:eu-repo/semantics/publishedVersio

Developing public health clinical decision support systems (CDSS) for the outpatient community in New York City: our experience

<p>Abstract</p> <p>Background</p> <p>Developing a clinically relevant set of quality measures that can be effectively used by an electronic health record (EHR) is difficult. Whether it is achieving internal consensus on relevant priority quality measures, communicating to EHR vendors' whose programmers generally lack clinical contextual knowledge, or encouraging implementation of EHR that meaningfully impacts health outcomes, the path is challenging. However, greater transparency of population health, better accountability, and ultimately improved health outcomes is the goal and EHRs afford us a realistic chance of reaching it in a scalable way.</p> <p>Method</p> <p>In this article, we summarize our experience as a public health government agency with developing measures for a public health oriented EHR in New York City in partnership with a commercial EHR vendor.</p> <p>Results</p> <p>From our experience, there are six key lessons that we share in this article that we believe will dramatically increase the chance of success. First, define the scope and build consensus. Second, get support from executive leadership. Third, find an enthusiastic and competent software partner. Fourth, implement a transparent operational strategy. Fifth, create and test the EHR system with real life scenarios. Last, seek help when you need it.</p> <p>Conclusions</p> <p>Despite the challenges, we encourage public health agencies looking to build a similarly focused public health EHR to create one both for improved individual patient as well as the larger population health.</p

Are youth mentoring programs good value-for-money? An evaluation of the Big Brothers Big Sisters Melbourne Program

Background : The Big Brothers Big Sisters (BBBS) program matches vulnerable young people with a trained, supervised adult volunteer as mentor. The young people are typically seriously disadvantaged, with multiple psychosocial problems.Methods : Threshold analysis was undertaken to determine whether investment in the program was a worthwhile use of limited public funds. The potential cost savings were based on US estimates of life-time costs associated with high-risk youth who drop out-of-school and become adult criminals. The intervention was modelled for children aged 10&ndash;14 years residing in Melbourne in 2004.Results : If the program serviced 2,208 of the most vulnerable young people, it would cost AUD 39.5 M. Assuming 50% were high-risk, the associated costs of their adult criminality would be AUD 3.3 billion. To break even, the program would need to avert high-risk behaviours in only 1.3% (14/1,104) of participants.Conclusion : This indicative evaluation suggests that the BBBS program represents excellent \u27value for money\u27.<br /

Point process time–frequency analysis of dynamic respiratory patterns during meditation practice

Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous system through its modulating influence on the heart beats. We propose a robust algorithm for quantifying instantaneous RSA as applied to heart beat intervals and respiratory recordings under dynamic breathing patterns. The blood volume pressure-derived heart beat series (pulse intervals, PIs) are modeled as an inverse Gaussian point process, with the instantaneous mean PI modeled as a bivariate regression incorporating both past PIs and respiration values observed at the beats. A point process maximum likelihood algorithm is used to estimate the model parameters, and instantaneous RSA is estimated via a frequency domain transfer function evaluated at instantaneous respiratory frequency where high coherence between respiration and PIs is observed. The model is statistically validated using Kolmogorov–Smirnov goodness-of-fit analysis, as well as independence tests. The algorithm is applied to subjects engaged in meditative practice, with distinctive dynamics in the respiration patterns elicited as a result. The presented analysis confirms the ability of the algorithm to track important changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states, reporting statistically significant increase in RSA gain as measured by our paradigm.National Institutes of Health (U.S.) (Grant R01-HL084502)National Institutes of Health (U.S.) (Grant R01-DA015644)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K01-AT00694-01

Opening the black box of under-health people: the case of Spain

ABSTRACT: The most famous modern definition of health was created during a Preamble to the Constitution of the World Health Organization in 1946: "Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." This definition has not been amended and, since then, many indicators have been proposed to measure health such as Self-Assessed Health (SAH) status. It provides an overall measure of a population's health based on individuals' personal perceptions of their own health. In this paper, we focus our analysis on "under-health" as the fact of having a level that falls behind the health requirements necessary to perform what is considered an "expected life based on Self Assessed Health". For Spain using the European Union Statistics on Income and Living Conditions (EU-SILC), we can confirm there exist under-healthy people by occupation, age group and sex. Additionally, under-healthy workers are most likely to be found among skilled agricultural, fishery workers and elementary occupations

Dense active matter model of motion patterns in confluent cell monolayers

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations. We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. Simulations and normal mode analysis perfectly match when tissue-level reorganisation occurs on times longer than the persistence time of cell motility. Our analytical model quantitatively matches measured velocity correlation functions over more than a decade with a single fitting parameter.Comment: updated version accepted for publication in Nat. Com

Fluctuations in granular gases

A driven granular material, e.g. a vibrated box full of sand, is a stationary system which may be very far from equilibrium. The standard equilibrium statistical mechanics is therefore inadequate to describe fluctuations in such a system. Here we present numerical and analytical results concerning energy and injected power fluctuations. In the first part we explain how the study of the probability density function (pdf) of the fluctuations of total energy is related to the characterization of velocity correlations. Two different regimes are addressed: the gas driven at the boundaries and the homogeneously driven gas. In a granular gas, due to non-Gaussianity of the velocity pdf or lack of homogeneity in hydrodynamics profiles, even in the absence of velocity correlations, the fluctuations of total energy are non-trivial and may lead to erroneous conclusions about the role of correlations. In the second part of the chapter we take into consideration the fluctuations of injected power in driven granular gas models. Recently, real and numerical experiments have been interpreted as evidence that the fluctuations of power injection seem to satisfy the Gallavotti-Cohen Fluctuation Relation. We will discuss an alternative interpretation of such results which invalidates the Gallavotti-Cohen symmetry. Moreover, starting from the Liouville equation and using techniques from large deviation theory, the general validity of a Fluctuation Relation for power injection in driven granular gases is questioned. Finally a functional is defined using the Lebowitz-Spohn approach for Markov processes applied to the linear inelastic Boltzmann equation relevant to describe the motion of a tracer particle. Such a functional results to be different from injected power and to satisfy a Fluctuation Relation.Comment: 40 pages, 18 figure

Survivin expression in oral squamous cell carcinoma

A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (P < 0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype

Be[com]ing a Teacher in Neoliberal Times: Visioning as Resistance in Teacher Education

Teacher education is under assault from the corporatization of public education. There is evidence that reductive, essentialized/ing discourses of standardization and compliance exert intense pressures on teacher education, and a market-based, audit culture constricts conceptions of the “good teacher”. Despite the pervasiveness of neoliberal discourses, little is known about how student teachers experience increased corporatization in education, or about how they act rather than are acted upon in this context. In examining these dynamics, we explore the following research questions: (a) How do student teachers make sense of neoliberal discourses in teaching? (b) How do student teachers experience the process of what Hammerness describes as “teacher visioning” in the context of neoliberal discourses? (c) What, if any, effect does visioning have on their responses to these discourses? We draw on qualitative data including focus groups, interviews, and document analysis from a group of early childhood student teachers enrolled in a public teacher education program and placed in field sites around eastern Massachusetts. Based on our findings, we argue that teacher visioning can, under certain circumstances, serve as an impetus for student teacher resistance to neoliberal pressures

Dark Matter from Minimal Flavor Violation

We consider theories of flavored dark matter, in which the dark matter particle is part of a multiplet transforming nontrivially under the flavor group of the Standard Model in a manner consistent with the principle of Minimal Flavor Violation (MFV). MFV automatically leads to the stability of the lightest state for a large number of flavor multiplets. If neutral, this particle is an excellent dark matter candidate. Furthermore, MFV implies specific patterns of mass splittings among the flavors of dark matter and governs the structure of the couplings between dark matter and ordinary particles, leading to a rich and predictive cosmology and phenomenology. We present an illustrative phenomenological study of an effective theory of a flavor SU(3)_Q triplet, gauge singlet scalar.Comment: 10 pages, 2 figures; v2: references added, minor changes to collider analysis, conclusions unchange