Miracle-dz/UniFAR-FTUs huggingface dataset:
Relative adrenal insufficiency in patients with septic shock: Comparison of low-dose and conventional corticotropin tests*

LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Define absolute and relative adrenal insufficiency. Explain the responses for low- and high-dose adrenocorticotropic hormone (ACTH)-stimulation tests. Use this information in a clinical setting. All of the authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective:To compare a low-dose (1 &mgr;g) corticotropin stimulation test with the more standard (250 &mgr;g) test for the diagnosis of relative adrenal insufficiency. Design:Diagnostic study. Setting:Thirty-one-bed mixed medico-surgical department of intensive care. Patients:Forty-six consecutive patients with septic shock. Interventions:Corticotropin stimulation tests (low-dose test, 1 &mgr;g, and standard 250-&mgr;g test), performed consecutively at an interval >4 hrs. Measurements and Main Results:In each test, serum cortisol levels were measured before (T0) and 30 (T30), 60 (T60), and 90 (T90) mins after corticotropin injection. The maximal increase in cortisol (&Dgr;max) was calculated as the difference between T0 and the highest cortisol value at T30, T60, or T90 and considered as adequate if >9 &mgr;g/dL (250 nmol/L). Nonresponders to the low-dose test had a lower survival rate than responders to both tests (27 vs. 47%, p = .06; Kaplan Meier curves). Interestingly, nonresponders to high-dose test received hydrocortisone treatment and had a similar survival to responders. Multivariable logistic regression disclosed that the response to the combined low-dose test and high-dose test was an independent predictor of survival (odds ratio 28.91, 95% confidence interval 1.81–462.70, p = .017), whereas basal or maximal cortisol levels in both tests were not. Conclusions:The low-dose test identified a subgroup of patients in septic shock with inadequate adrenal reserve who had a worse outcome and would have been missed by the high-dose test. These patients may also benefit from glucocorticoid replacement therapy.
Types of employment and health in the European union: changes from 1995 to 2000.

BACKGROUND This study compares associations between types of employment and health indicators in the Second (ES1995) and the Third European Survey on Working Conditions (ES2000) by gender, adjusting for individual and country-level confounders. METHODS Two cross-sectional surveys of a representative sample of the European Union (EU) total active population (n=15,146 workers in ES1995 and n=21,703 workers in ES2000). Based on their comparability in both surveys four health indicators were considered: job dissatisfaction, stress, fatigue and backache. RESULTS Non-permanent employment reported high percentages of job dissatisfaction but low levels of stress. Small employers were more likely to report fatigue and stress but less likely to report job dissatisfaction. Sole traders were more likely to report fatigue and backache. Workers in full-time employment almost always reported worse levels of health indicators than part-time. Two exceptions for part-time were found: temporary employment regarding job dissatisfaction, and in ES2000, sole traders with regard to job dissatisfaction, fatigue and backache. By and large, results by gender were similar in both surveys, although the magnitude of associations decreased in ES2000. Associations remained unchanged after adjustment. CONCLUSION This study has compared for the first time the associations between various types of employment and four health indicators for the EU in ES1995 and ES2000, by gender. Overall, a slight increase in all health indicators was observed in the ES2000 compared to ES1995, and results were very consistent between both surveys. Similar findings in both surveys suggest that causal interpretation may be enhanced.
Response Patterns of EGb 761® in Alzheimer’s Disease: Influence of Neuropsychological Profiles

We conducted an exploratory analysis of the influence of baseline neuropsychological (NP) profiles on the effect of EGb 761 (definition see editorial) in Alzheimer's disease (AD). Using this perspective, we stratified the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled study with 120 mg EGb 761 based on cut-off points applied to naming and constructional praxis items of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Mean changes over baseline and percentage of responders in each NP group and overall efficacy were analyzed, using the ADAS-Cog subscale as outcome measurements for assessing cognitive performance and the Geriatric Evaluation using the Relative's Rating Instrument (GERRI) to measure social functioning. Three subgroups were identified: (1) right AD (RAD) subgroup, including 83 patients with primarily visual-constructional impairment; (2) left AD (LAD) with 25 patients showing predominant verbal deficits; (3) general AD (GAD) including 60 patients impaired in both cognitive domains. At the endpoint, the EGb 761 group of RAD showed an improvement of 1.7 points according to ADAS-Cog and 0.15 points according to GERRI, while the placebo group worsened by 1.3 and 0.02 points, respectively. The LAD patients worsened regardless of treatment; however, to a lesser degree in those receiving EGb 761 as assessed by the increase of 4.7 ADAS-Cog points and 0.13 GERRI points compared to 6.8 points and 0.20 points, respectively, for placebo. In GAD, the EGb 761 group showed minimal changes, whereas the placebo group slightly worsened on both assessments, resulting in favorable treatment differences of 1.6 ADAS-Cog points and 0.23 GERRI points. Retrospective analysis of overall efficacy indicated that a quantitative treatment effect favorable to EGb 761 could be observed in cognitive performance (p = 0.04) and social functioning (p = 0.02), even taking NP differences and baseline severity into account. However, qualitative EGb 761 effects could greatly depend on NP profiles--improvement could be expected with RAD patients, while EGb 761 effect should be considered more in terms of stabilization for GAD and delayed worsening for LAD population.
Online Model Selection Based on the Variational Bayes

The Bayesian framework provides a principled way of model selection. This framework estimates a probability distribution over an ensemble of models, and the prediction is done by averaging over the ensemble of models. Accordingly, the uncertainty of the models is taken into account, and complex models with more degrees of freedom are penalized. However, integration over model parameters is often intractable, and some approximation scheme is needed. Recently, a powerful approximation scheme, called the variational bayes (VB) method, has been proposed. This approach defines the free energy for a trial probability distribution, which approximates a joint posterior probability distribution over model parameters and hidden variables. The exact maximization of the free energy gives the true posterior distribution. The VB method uses factorized trial distributions. The integration over model parameters can be done analytically, and an iterative expectation-maximization-like algorithm, whose convergence is guaranteed, is derived. In this article, we derive an online version of the VB algorithm and prove its convergence by showing that it is a stochastic approximation for finding the maximum of the free energy. By combining sequential model selection procedures, the online VB method provides a fully online learning method with a model selection mechanism. In preliminary experiments using synthetic data, the online VB method was able to adapt the model structure to dynamic environments.
Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies

Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis. Lupus (2007) 16, 259—264.
Filterability of mixtures of sickle and normal erythrocytes

We investigated the deformability of sickle (SS) cells from 25 patients and mixtures of these SS cells with blood type‐compatible normal (AA) cells, using a nickel mesh filtration system, with the aim of determining optimal goals for exchange therapy. We found that for air‐equilibrated SS/AA cell mixtures the fraction of dense cells (MCHC >37 g/dl) is the determinant factor in filterability and that the dense cells contribute in a linear fashion to the loss of filtration up to 15% dense cells (y = ‐4.41 × + 98.23, r = 0.945, P < 0.0001). The slope of this effect is approximately 25 times steeper than that of the relationship between filtration and percent nondense (MCHC < 37/g/dl) SS cells (y = ‐0.17x +106.53, r = 0.772, P < 0.0001). A comparison of the proportion of high fluorescence reticulocytes to total reticulocytes (HFR ratio), indicating an elevation of immature reticulocytes, between six nontransfused patients and six exchange‐transfused patients showed significant higher values in the nontransfused individuals (0.154 ± 0.051 versus 0.070 ± 0.054, P < 0.003). These results may have implications regarding targets for exchange transfusion therapy. Further studies of the effect on transfusion, both simple and exchange, on the numbers of dense cells and the proportions and populations of reticulocytes and the rheological characteristics of the erythrocyte subpopulations seems warranted.
Contexts of risk and networks of protection: NYC West Indian immigrants' perceptions of migration and vulnerability to sexually transmitted diseases

To generate insights into how migration shapes sexual risk and protection, we interviewed 36 female and 20 male West Indian immigrants attending a public sexually transmitted disease clinic in Brooklyn, New York, between 2004 and 2005. Migration theory suggests that shifts in sexual partnership patterns, bi-directional travel and changes in sexual norms may alter risk. We found evidence of sexual mixing across ethnic groups: a large proportion of participants' partners were not born in the West Indies, despite what is expected among first generation immigrants. Recent travel ‘home’, another potential source of risk, was uncommon. In open-ended interviews, two themes around sexual and social networks emerged. First, immigrants believed that access to wider, more anonymous sexual networks in New York City (NYC) and the weakening of social controls that limit multiple partnerships (especially for women) promoted greater risk. Second, immigrants experienced greater opportunities for protection in NYC, both through exposure to safer sex messages and availability of condoms. Reported changes in their own condom use, however, were not attributed to migration. West Indian immigrants' risk in NYC may be driven by access to wider sexual networks but failure to alter reliance on ‘networks of knowledge’ for protection.
Influence of Hospital Ownership and Governance structure on Maternal Delivery Services

VIII TABLE OF CONTENTS . IX LIST OF TABLES . XIII LIST OF FIGURES . XV ABBREVIATIONS/ACRONYMS . XVI DEFINITION OF OPERATIONAL TERMS . XIX CHAPTER 1: INTRODUCTION . 1 BACKGROUND . 2 1.1.1. THE HEALTH SYSTEM . 2 1.1. 2. HEALTH SERVICE DELIVERY GOALS . 7 1.1.3. THE HOSPITAL . 10 1.1. 4. HOSPITAL GOVERNANCE . 12 1.1. 5. MATERNAL DELIVERY SERVICES . 14 STATEMENT OF RESEARCH PROBLEM . 15 GENERAL OBJECTIVE . 19 1.3. 1. SPECIFIC OBJECTIVES . 19 SIGNIFICANCE OF STUDY . 19 CHAPTER 2: LITERATURE REVIEW . 22 INTRODUCTION . 22 THE HEALTH SYSTEM . 22 EQUITY IN THE DELIVERY OF MATERNAL DELIVERY SERVICES. 26 EFFECTIVENESS . 29 2.3. 1. HOSPITAL EFFICIENCY . 31 HEALTH SYSTEM GOVERNANCE . 33 2.4. 1. ASSESSING HEALTH SYSTEM GOVERNANCE . 35
In mice, the muscle weakness due to age is absent during stretching.

1. The contractile force was compared in isolated soleus muscles from young (2.5‐8 months old) and aged (28‐31 months old) mice. Force was measured at 25 degrees C during isometric tetanic contractions during isovelocity stretching and shortening contractions. 2. The normalized isometric force was lower by 13.3% in muscles from aged mice. Muscles from young and aged mice produced 0.951 +/‐ 0.031 N mg‐1 (n = 12) and 0.824 +/‐ 0.048 N mg‐1 (n = 9) respectively. The relaxation time, from 90 to 10% of the tetanic force, of muscles from aged mice was 102.1 +/‐ 3.7 ms (n = 6), which was longer than that for muscles from young mice, 84.4 +/‐ 3.8 ms (n = 6) (means +/‐ S.E.M.). 3. The force during shortening was also reduced in muscles from aged animals by the same proportion as the isometric force. Therefore the force during shortening relative to the isometric force was the same in muscles from young and aged mice. 4. During rapid stretching soleus muscles from aged mice produced a similar force to those from young mice. Therefore stretch can remove the weakness in muscles of aged mice. 5. These changes in muscles from aged mice are similar to those produced when inorganic phosphate (Pi) levels are raised, in skinned rabbit psoas fibres, or during fatigue or with low intracellular pH (pHi), in frog muscle. It is possible therefore that the force loss due to ageing may be due to a higher Pi level or a lower pHi.
DNA Methylation Profiles in Placenta and Its Association with Gestational Diabetes Mellitus

Abstract Emerging evidences indicate that placenta plays a critical role in gestational diabetes mellitus (GDM). DNA methylation could be associated with altered placental development and functions. This study is to uncover the genome-wide DNA methylation patterns in this disorder. DNA methylation was measured at >385 000 CpG sites using methylated DNA immunoprecipitation (MeDIP) and a huamn CpG island plus promoter microarray. We totally identified 6 641 differentially methylated regions (DMRs) targeting 3 320 genes, of which 2 729 DMRs targeting 1 399 genes, showed significant hypermethylation in GDM relative to the controls, whereas 3 912 DMRs targeting 1 970 genes showed significant hypomethylation. Functional analysis divided these genes into different functional networks, which mainly involved in the pathways of cell growth and death regulation, immune and inflammatory response and nervous system development. In addition, the methylation profiles and expressions of 4 loci (RBP4, GLUT3, Resistin and PPARα) were validated by BSP for their higher log2 ratio and potential functions with energy metabolism. This study demonstrates aberrant patterns of DNA methylation in GDM which may be involved in the pathophysiology of GDM and reflect the fetal development. Future work will assess the potential prognostic and therapeutic value for these findings in GDM.
Viscoelasticity Mapping by Identification of Local Shear Wave Dynamics

Estimation of soft tissue elasticity is of interest in several clinical applications. For instance, tumors and fibrotic lesions are notoriously stiff compared with benign tissue. A fully quantitative measure of lesion stiffness can be obtained by shear wave (SW) elastography. This method uses an acoustic radiation force to produce laterally propagating SWs that can be tracked to obtain the velocity, which in turn is related to Young’s modulus. However, not only elasticity, but also viscosity plays an important role in the propagation process of SWs. In fact, viscosity itself is a parameter of diagnostic value for the detection and characterization of malignant lesions. In this paper, we describe a new method that enables imaging viscosity from SW elastography by local model-based system identification. By testing the method on simulated data sets and performing in vitro experiments, we show that the ability of the proposed technique to generate parametric maps of the viscoelastic material properties from SW measurements, opening up new possibilities for noninvasive tissue characterization.
Cognitive behavioural therapy from the perspective of clients with mild intellectual disabilities: a qualitative investigation of process issues.

BACKGROUND Clinicians working with clients who have mild intellectual disabilities (IDs) have shown growing enthusiasm for using a cognitive behavioural approach, amid increasing evidence of good treatment outcomes for this client group. However, very little is known about the views and experiences of clients with IDs who have undergone cognitive behavioural therapy. This study aims to explore the perspective of these clients. METHODS Fifteen participants with borderline to mild IDs and problems of anxiety, depression and anger were interviewed regarding their experience of cognitive behavioural therapy (CBT). Two semi-structured interviews were carried out in the first phase of therapy between session four and session nine. An interpretive phenomenological approach was taken to seek out themes from participants' own personal accounts. RESULTS Participants valued the opportunity to talk about problems with their therapist and benefitted from therapeutic relationships characterised by warmth, empathy and validation. Participants identified areas of positive change; however, many thought that this may be short lived or not maintained beyond discharge. CONCLUSIONS The supportive aspects of therapeutic relationships were particularly important to participants undergoing CBT. The clinical implications are considered.
Personal localization of task force members in urban environments

This paper presents a tightly-coupled INS/GNSS integration for personal navigation systems using foot-mounted sensors. Our precise relative positioning INS based on high accurate Zero-Velocity-Updates (ZUPTs) is fused with GNSS pseudo-range and doppler measurements for absolute position and heading estimation. Unique is the decision depending on the classified motion state if doppler measurements improve the accuracy of the navigation solution. In addition, the integrity of the GNSS signals are checked. The good knowledge of our precise relative positioning inertial system is used to detect and exclude GNSS measurements with high multipath errors. This is essential for robust personal localization in dense urban environments. Detailed analysis of a test walk in urban canyons with two outdoor-indoor transitions show the high performance and robustness of our proposed approach. Our system is appropriate for the localization of task force members due to the accuracy and robustness of the real-time capable navigation solution and the independence of pre-installed infrastructure.
The HSP90 Inhibitor XL888 Overcomes BRAF Inhibitor Resistance Mediated through Diverse Mechanisms

Purpose: The clinical use of BRAF inhibitors is being hampered by the acquisition of drug resistance. This study shows the potential therapeutic use of the HSP90 inhibitor (XL888) in six different models of vemurafenib resistance. Experimental Design: The ability of XL888 to inhibit growth and to induce apoptosis and tumor regression of vemurafenib-resistant melanoma cell lines was shown in vitro and in vivo. A novel mass spectrometry–based pharmacodynamic assay was developed to measure intratumoral HSP70 levels following HSP90 inhibition in melanoma cell lines, xenografts, and melanoma biopsies. Mechanistic studies were carried out to determine the mechanism of XL888-induced apoptosis. Results: XL888 potently inhibited cell growth, induced apoptosis, and prevented the growth of vemurafenib-resistant melanoma cell lines in 3-dimensional cell culture, long-term colony formation assays, and human melanoma mouse xenografts. The reversal of the resistance phenotype was associated with the degradation of PDGFRβ, COT, IGFR1, CRAF, ARAF, S6, cyclin D1, and AKT, which in turn led to the nuclear accumulation of FOXO3a, an increase in BIM (Bcl-2 interacting mediator of cell death) expression, and the downregulation of Mcl-1. In most resistance models, XL888 treatment increased BIM expression, decreased Mcl-1 expression, and induced apoptosis more effectively than dual mitogen-activated protein–extracellular signal–regulated kinase/phosphoinositide 3-kinase (MEK/PI3K) inhibition. Conclusions: HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. Clin Cancer Res; 18(9); 2502–14. ©2012 AACR.
Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis.

The two major forms of infantile persistent hyperinsulinemic hypoglycemia require different treatments, but are difficult to differentiate during surgery. Indeed, one is characterized by focal adenomatous hyperplasia often macroscopically invisible, whereas the other consists of a diffuse, but discreet, beta-cell abnormality. We evaluated, in a large series of persistent hyperinsulinemic hypoglycemia, the reliability of two criteria in differentiating these two forms: the mean beta-cell nuclear radius (MNR) and the beta-cell nuclear crowding, i.e. the number of nuclei per 1000 micron 2 beta-cell (BCNC). The values of the largest MNR and of BCNC in cases bearing a focal lesion (respectively, 3.27 microns +/- 0.25 and 14.62 +/- 1.78) were significantly different from those in the diffuse pathology (4.25 microns +/- 0.43 and 10.00 +/- 1.55). Setting the threshold value of MNR at 3.70 microns and that of BCNC at 12.00 enabled correct classification of 90.9% of the diffuse and 100% of the focal forms. beta-Cell nuclear analysis can thus contribute to a subclassification of the syndrome, not allowed by clinical or biological data. If performed during surgery it could help in determining the extent of pancreatectomy necessary to cure the patient, as the diffuse form, with abnormal nuclei in the whole pancreas, requires subtotal to near-total pancreatectomy, whereas the focal form, devoid of abnormal insular beta-cell nuclei, can be cured by partial pancreatectomy.