Automatic, fast and robust characterization of noise distributions for diffusion MRI

Knowledge of the noise distribution in magnitude diffusion MRI images is the centerpiece to quantify uncertainties arising from the acquisition process. The use of parallel imaging methods, the number of receiver coils and imaging filters applied by the scanner, amongst other factors, dictate the resulting signal distribution. Accurate estimation beyond textbook Rician or noncentral chi distributions often requires information about the acquisition process (e.g. coils sensitivity maps or reconstruction coefficients), which is not usually available. We introduce a new method where a change of variable naturally gives rise to a particular form of the gamma distribution for background signals. The first moments and maximum likelihood estimators of this gamma distribution explicitly depend on the number of coils, making it possible to estimate all unknown parameters using only the magnitude data. A rejection step is used to make the method automatic and robust to artifacts. Experiments on synthetic datasets show that the proposed method can reliably estimate both the degrees of freedom and the standard deviation. The worst case errors range from below 2% (spatially uniform noise) to approximately 10% (spatially variable noise). Repeated acquisitions of in vivo datasets show that the estimated parameters are stable and have lower variances than compared methods.Comment: v2: added publisher DOI statement, fixed text typo in appendix A

New strategies to measure intracellular sodium concentrations

Fluorescent ion indicators are widely used to measure ion concentrations in living cells. However, despite considerable efforts in synthesizing new compounds, no ratiometric sodium indicator is available that can be excited at visible wavelengths. Ratiometric indicators have an advantage in that measured fluorescence intensities can be corrected for fluctuations of the indicator concentration and the illumination intensity, which is not possible when non-ratiometric indicators are used. One way to circumvent this problem is to measure fluorescence lifetimes, which are independent of these factors. Another way to overcome the disadvantages of a non-ratiometric indicator dye is to embed it, together with a reference dye, into nanoparticles. By relating the indicator fluorescence to the fluorescence of the reference dye, inhomogeneities in the nanosensor concentration or the illumination intensity can be cancelled out reliably. In this study we compare the benefits and drawbacks of these approaches. © 2010 Copyright SPIE - The International Society for Optical Engineering

Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis

Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies. Copyright (c) 2006 S. Karger AG, Basel

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6

Background: Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV. Methods: We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619. Results: OAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, U73122, a blocker of DAG synthesis, inhibited acute HPV whereas U73343, the inactive form of U73122, had no effect on HPV. Conclusion: These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG

Global Analysis of the Higgs Candidate with Mass ~ 125 GeV

We analyze the properties of the Higgs candidate with mass ~ 125 GeV discovered by the CMS and ATLAS Collaborations, constraining the possible deviations of its couplings from those of a Standard Model Higgs boson. The CMS, ATLAS and Tevatron data are compatible with Standard Model couplings to massive gauge bosons and fermions, and disfavour several types of composite Higgs models unless their couplings resemble those in the Standard Model. We show that the couplings of the Higgs candidate are consistent with a linear dependence on particle masses, scaled by the electroweak scale ~ 246 GeV, the power law and the mass scale both having uncertainties ~ 20%.Comment: 22 pages, 9 figures, v2 incorporates experimental data released during July 2012 and corrected (and improved) treatment of mass dependence of coupling

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

<p>Abstract</p> <p>Background</p> <p>Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies.</p> <p>Objectives</p> <p>Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis.</p> <p>Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication.</p> <p>Design</p> <p>The <b>a</b>pproach to a <b>qua</b>ntitative <b>f</b>ollow-up <b>o</b>f <b>n</b>on-<b>t</b>hyroidal <b>i</b>llness <b>s</b>yndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes.</p> <p>The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00591032</p

Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons

In many strongly-interacting models of electroweak symmetry breaking the lowest-lying observable particle is a pseudo-Goldstone boson of approximate scale symmetry, the pseudo-dilaton. Its interactions with Standard Model particles can be described using a low-energy effective nonlinear chiral Lagrangian supplemented by terms that restore approximate scale symmetry, yielding couplings of the pseudo-dilaton that differ from those of a Standard Model Higgs boson by fixed factors. We review the experimental constraints on such a pseudo-dilaton in light of new data from the LHC and elsewhere. The effective nonlinear chiral Lagrangian has Skyrmion solutions that may be identified with the `electroweak baryons' of the underlying strongly-interacting theory, whose nature may be revealed by the properties of the Skyrmions. We discuss the finite-temperature electroweak phase transition in the low-energy effective theory, finding that the possibility of a first-order electroweak phase transition is resurrected. We discuss the evolution of the Universe during this transition and derive an order-of-magnitude lower limit on the abundance of electroweak baryons in the absence of a cosmological asymmetry, which suggests that such an asymmetry would be necessary if the electroweak baryons are to provide the cosmological density of dark matter. We revisit estimates of the corresponding spin-independent dark matter scattering cross section, with a view to direct detection experiments.Comment: 34 pages, 4 figures, additional references adde

Determinants of outcome in operatively and non-operatively treated Weber-B ankle fractures

Introduction: Treatment of ankle fractures is often based on fracture type and surgeon's individual judgment. Literature concerning the treatment options and outcome are dated and frequently contradicting. The aim of this study was to determine the clinical and functional outcome after AO-Weber B-type ankle fractures in operatively and conservatively treated patients and to determine which factors influenced outcome. Patients and methods: A retrospective cohort study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and treatment characteristics were recorded. Clinical and functional outcome was measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score (VAS) for overall satisfaction (range 0-10). Results: Eighty-two patients were treated conservatively and 103 underwent operative treatment. The majority was female. Most conservatively treated fractures were AO-Weber B1.1 type fractures. Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type SER-4) were predominantly treated operatively. The outcome scores in the non-operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was independently negatively affected by age, affected side, BMI, fibular displacement, and duration of plaster immobilization. In the surgically treated group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with outcome negatively influenced by duration of plaster immobilization. Conclusion: Treatment selection based upon stability and surgeon's judgment led to overall good clinical outcome in both treatment groups. Reducing the cast immobilization period may further improve outcome