The value of implementation and the value of information: combined and uneven development

<i>Aim</i>: In a budget-constrained health care system, the decision to invest in strategies to improve the implementation of cost-effective technologies must be made alongside decisions regarding investment in the technologies themselves and investment in further research. This article presents a single, unified framework that simultaneously addresses the problem of allocating funds between these separate but linked activities. <i>Methods</i>: The framework presents a simple 4-state world where both information and implementation can be either at the current level or "perfect". Through this framework, it is possible to determine the maximum return to further research and an upper bound on the value of adopting implementation strategies. The framework is illustrated through case studies of health care technologies selected from those previously considered by the UK National Institute for Health and Clinical Excellence (NICE). <i>Results</i>: Through the case studies, several key factors that influence the expected values of perfect information and perfect implementation are identified. These factors include the maximum acceptable cost-effectiveness ratio, the level of uncertainty surrounding the adoption decision, the expected net benefits associated with the technologies, the current level of implementation, and the size of the eligible population. <i>Conclusions</i>: Previous methods for valuing implementation strategies have not distinguished the value of efficacy research and the value of strategies to change the level of implementation. This framework demonstrates that the value of information and the value of implementation can be examined separately but simultaneously in a single framework. This can usefully inform policy decisions about investment in health care services, further research, and adopting implementation strategies that are likely to differ between technologies

Studies on the clinical significance of nonesterified and total cholesterol in urine

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean±2 SD) of 0.2–2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3–3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers

Os odontoideum with bipartite atlas and segmental instability: a case report

We report on the case of a 15-year-old adolescent who presented with a transient paraplegia and hyposensibility of the upper extremities after sustaining a minor hyperflexion trauma to the cervical spine. Neuroimaging studies revealed atlantoaxial dislocation and ventral compression of the rostral spinal cord with increased cord signal at C1/C2 levels caused by an os odontoideum, as well as anterior and posterior arch defects of the atlas. The patient underwent closed reduction and posterior atlantoaxial fusion. We describe the association of an acquired instability secondary to an os odontoideum with an anteroposterior spondyloschisis of the atlas and its functional result after 12 months. The rare coincidence of both lesions indicates a multiple malformation of the upper cervical spine and supports the theory of an embryologic genesis of os odontoideum

An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature

BACKGROUND: Glucocorticoid resistance is a rare, sporadic or familial condition caused by mutation of the gene encoding the glucocorticoid receptor (GR). Clinically it is characterized by symptoms developed due to local, tissue-specific, or generalized partial insensitivity to glucocorticoids. CASE PRESENTATION: A 31-year-old woman was evaluated because of infertility at the Endocrine Unit of the 2nd Department of Medicine, Semmelweis University. During her laboratory investigations, elevated serum and salivary cortisol were observed which failed to be suppressed after administration of 1 mg dexamethasone. 24 h urinary cortisol was increased, but a normal midnight serum cortisol was detected suggesting a maintained circadian rhythm. Plasma dehydroepiandrosterone-sulfate and androstendione levels were also elevated. Repeated plasma ACTH measurements indicated slightly elevated or normal values. Bone mineral density was normal. All laboratory results confirmed the diagnosis of glucocorticoid resistance. Genetic counseling followed by Sanger sequencing of the coding region of the gene encoding human glucocorticoid receptor was performed and a missense mutation (Arg714Gln, R714Q) in a heterozygous form was detected. Following family screening, the same mutation was found in her clinically-healthy 35-year-old sister who had no fertility problems.This variant was not detected in more than 60 patients and controls tested either for glucocorticoid resistance or Cushing's syndrome in our Laboratory and it was absent in Exome Variant Server, HumanGene Mutation Database and ExAC databases. CONCLUSIONS: Our case fulfils the diagnostic criteria of glucocorticoid resistance, also named Chrousos syndrome. The glucocorticoid receptor gene mutation detected in our patient has been already reported in a 2-year-old child with hypoglycaemia, hypokalaemia, hypertension and premature puberty. These distinct phenotypes may suggest that other factors may modify the functional consequences of the R714Q variant of GR

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Overview of (pro-)Lie group structures on Hopf algebra character groups

Character groups of Hopf algebras appear in a variety of mathematical and physical contexts. To name just a few, they arise in non-commutative geometry, renormalisation of quantum field theory, and numerical analysis. In the present article we review recent results on the structure of character groups of Hopf algebras as infinite-dimensional (pro-)Lie groups. It turns out that under mild assumptions on the Hopf algebra or the target algebra the character groups possess strong structural properties. Moreover, these properties are of interest in applications of these groups outside of Lie theory. We emphasise this point in the context of two main examples: The Butcher group from numerical analysis and character groups which arise from the Connes--Kreimer theory of renormalisation of quantum field theories.Comment: 31 pages, precursor and companion to arXiv:1704.01099, Workshop on "New Developments in Discrete Mechanics, Geometric Integration and Lie-Butcher Series", May 25-28, 2015, ICMAT, Madrid, Spai

Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis

Citation: Hanzlicek, G. A., Raghavan, R. K., Ganta, R. R., & Anderson, G. A. (2016). Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis. Plos One, 11(3), 13. doi:10.1371/journal.pone.0151924The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (>0.7). The relevance of climatological factors for bovine anaplasmosis is discussed

Centre of pressure characteristics in normal, planus and cavus feet

Background The aim of this study was to compare centre of pressure (COP) characteristics between healthy adults with normal, planus or cavus feet who were allocated to groups based on reliable foot posture measurement techniques. Methods Ninety-two healthy adult participants (aged 18 to 45) were recruited and classified as either normal (n = 35), pes planus (n = 31) or pes cavus (n = 26) based on Foot Posture Index, Arch Index and normalised navicular height truncated measurements. Barefoot walking trials were conducted using an emed®-x 400 plantar pressure system (Novel GmbH, Munich, Germany). Average, maximum, minimum and range (difference between maximum and minimum) values were calculated for COP velocity and lateral-medial force index during loading response, midstance, terminal stance and pre-swing phases of stance. The COP excursion index was also calculated. One-way analyses of variance were used to compare the three foot posture groups. Results The cavus foot exhibited the slowest average and minimum COP velocity during terminal stance, but this pattern was reversed during pre-swing, when the cavus foot exhibited the fastest maximum COP velocity. The planus foot exhibited the smallest lateral medial force index range during terminal stance. There were no differences between the groups for COP excursion index. Conclusion These findings indicate that there are differences in COP characteristics between foot postures, which may represent different mechanisms for generating force to facilitate forward progression of the body during the propulsive phases of gait

Of Toasters and Molecular Ticker Tapes

Experiments in systems neuroscience can be seen as consisting of three steps: (1) selecting the signals we are interested in, (2) probing the system with carefully chosen stimuli, and (3) getting data out of the brain. Here I discuss how emerging techniques in molecular biology are starting to improve these three steps. To estimate its future impact on experimental neuroscience, I will stress the analogy of ongoing progress with that of microprocessor production techniques. These techniques have allowed computers to simplify countless problems; because they are easier to use than mechanical timers, they are even built into toasters. Molecular biology may advance even faster than computer speeds and has made immense progress in understanding and designing molecules. These advancements may in turn produce impressive improvements to each of the three steps, ultimately shifting the bottleneck from obtaining data to interpreting it