Prostate specific antigen doubling time as auxiliary end point in hormone refractory prostatic carcinoma

In hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa.

Standard vs. point-of-care measurement of fibrinogen: potential impact on clinical decisions

Intraoperative major bleeding is a common complication during surgery and can lead to the transfusion of blood products and/or procoagulant drugs. This is a therapeutic challenge, and adherence to guidelines is desirable to preserve blood product resources. The intraoperative administration of fibrinogen concentrate, a pro-coagulant drug, in bleeding patients might reduce the use and therefore the risks associated with blood products.

Asymptotic freedom, dimensional transmutation, and an infrared conformal fixed point for the δ-function potential in one-dimensional relativistic quantum mechanics

We consider the Schrödinger equation for a relativistic point particle in an external one-dimensional δ-function potential. Using dimensional regularization, we investigate both bound and scattering states, and we obtain results that are consistent with the abstract mathematical theory of self-adjoint extensions of the pseudodifferential operator H=p2+m2−−−−−−−√. Interestingly, this relatively simple system is asymptotically free. In the massless limit, it undergoes dimensional transmutation and it possesses an infrared conformal fixed point. Thus it can be used to illustrate nontrivial concepts of quantum field theory in the simpler framework of relativistic quantum mechanics.

Risk assessment in the first fifteen minutes: a prospective cohort study of a simple physiological scoring system in the emergency department

Introduction The survival of patients admitted to an emergency department is determined by the severity of acute illness and the quality of care provided. The high number and the wide spectrum of severity of illness of admitted patients make an immediate assessment of all patients unrealistic. The aim of this study is to evaluate a scoring system based on readily available physiological parameters immediately after admission to an emergency department (ED) for the purpose of identification of at-risk patients. Methods This prospective observational cohort study includes 4,388 consecutive adult patients admitted via the ED of a 960-bed tertiary referral hospital over a period of six months. Occurrence of each of seven potential vital sign abnormalities (threat to airway, abnormal respiratory rate, oxygen saturation, systolic blood pressure, heart rate, low Glasgow Coma Scale and seizures) was collected and added up to generate the vital sign score (VSS). VSSinitial was defined as the VSS in the first 15 minutes after admission, VSSmax as the maximum VSS throughout the stay in ED. Occurrence of single vital sign abnormalities in the first 15 minutes and VSSinitial and VSSmax were evaluated as potential predictors of hospital mortality. Results Logistic regression analysis identified all evaluated single vital sign abnormalities except seizures and abnormal respiratory rate to be independent predictors of hospital mortality. Increasing VSSinitial and VSSmax were significantly correlated to hospital mortality (odds ratio (OR) 2.80, 95% confidence interval (CI) 2.50 to 3.14, P < 0.0001 for VSSinitial; OR 2.36, 95% CI 2.15 to 2.60, P < 0.0001 for VSSmax). The predictive power of VSS was highest if collected in the first 15 minutes after ED admission (log rank Chi-square 468.1, P < 0.0001 for VSSinitial;,log rank Chi square 361.5, P < 0.0001 for VSSmax). Conclusions Vital sign abnormalities and VSS collected in the first minutes after ED admission can identify patients at risk of an unfavourable outcome.

Screening and prediction of erosive potential

The literature on the erosive potential of drinks and other products is summarised, and aspects of the conduct of screening tests as well as possible correlations of the erosive potential with various solution parameters are discussed. The solution parameters that have been suggested as important include pH, acid concentration (with respect to buffer capacity and concentration of undissociated acid), degree of saturation, calcium and phosphate concentrations, and inhibitors of erosion. Based on the available data, it is concluded that the dominant factor in erosion is pH. The effect of buffer capacity seems to be pH dependent. The degree of saturation probably has a non-linear relationship with erosion. While calcium at elevated concentrations is known to reduce erosion effectively, it is not known whether it is important at naturally occurring concentrations. Fluoride at naturally occurring concentrations is inversely correlated with erosive potential, but phosphate is probably not. Natural plant gums, notably pectin, do not inhibit erosion, so they are unlikely to interfere with the prediction of erosive potential. The non-linearity of some solution factors and interactions with pH need to be taken into account when developing multivariate models for predicting the erosive potential of different solutions. Finally, the erosive potential of solutions towards enamel and dentine might differ.

Self-assembly of focal point oligo-catechol ethylene glycol dendrons on titanium oxide surfaces: adsorption kinetics, surface characterization, and nonfouling properties

This work covers the synthesis of second-generation, ethylene glycol dendrons covalently linked to a surface anchor that contains two, three, or four catechol groups, the molecular assembly in aqueous buffer on titanium oxide surfaces, and the evaluation of the resistance of the monomolecular adlayers against nonspecific protein adsorption in contact with full blood serum. The results were compared to those of a linear poly(ethylene glycol) (PEG) analogue with the same molecular weight. The adsorption kinetics as well as resulting surface coverages were monitored by ex situ spectroscopic ellipsometry (VASE), in situ optical waveguide lightmode spectroscopy (OWLS), and quartz crystal microbalance with dissipation (QCM-D) investigations. The expected compositions of the macromolecular films were verified by X-ray photoelectron spectroscopy (XPS). The results of the adsorption study, performed in a high ionic strength ("cloud-point") buffer at room temperature, demonstrate that the adsorption kinetics increase with increasing number of catechol binding moieties and exceed the values found for the linear PEG analogue. This is attributed to the comparatively smaller and more confined molecular volume of the dendritic macromolecules in solution, the improved presentation of the catechol anchor, and/or their much lower cloud-point in the chosen buffer (close to room temperature). Interestingly, in terms of mechanistic aspects of "nonfouling" surface properties, the dendron films were found to be much stiffer and considerably less hydrated in comparison to the linear PEG brush surface, closer in their physicochemical properties to oligo(ethylene glycol) alkanethiol self-assembled monolayers than to conventional brush surfaces. Despite these differences, both types of polymer architectures at saturation coverage proved to be highly resistant toward protein adsorption. Although associated with higher synthesis costs, dendritic macromolecules are considered to be an attractive alternative to linear polymers for surface (bio)functionalization in view of their spontaneous formation of ultrathin, confluent, and nonfouling monolayers at room temperature and their outstanding ability to present functional ligands (coupled to the termini of the dendritic structure) at high surface densities.

ECM versus ICP for point registration

Iterative Closest Point (ICP) is a widely exploited method for point registration that is based on binary point-to-point assignments, whereas the Expectation Conditional Maximization (ECM) algorithm tries to solve the problem of point registration within the framework of maximum likelihood with point-to-cluster matching. In this paper, by fulfilling the implementation of both algorithms as well as conducting experiments in a scenario where dozens of model points must be registered with thousands of observation points on a pelvis model, we investigated and compared the performance (e.g. accuracy and robustness) of both ICP and ECM for point registration in cases without noise and with Gaussian white noise. The experiment results reveal that the ECM method is much less sensitive to initialization and is able to achieve more consistent estimations of the transformation parameters than the ICP algorithm, since the latter easily sinks into local minima and leads to quite different registration results with respect to different initializations. Both algorithms can reach the high registration accuracy at the same level, however, the ICP method usually requires an appropriate initialization to converge globally. In the presence of Gaussian white noise, it is observed in experiments that ECM is less efficient but more robust than ICP.

Clazosentan: prevention of cerebral vasospasm and the potential to overcome infarction

Cerebral vasospasm is a common complication occurring after aneurysmal subarachnoid hemorrhage (SAH). It is recognized as a leading preventable cause of morbidity and mortality in this patient group, but its management is challenging, and new treatments are needed. Clazosentan is an endothelin receptor antagonist designed to prevent endothelin-mediated cerebral vasospasm. Vajkoczy et al. (Neurosurg 103:9-17, 2005) initially demonstrated that clazosentan reduced moderate/severe angiographically proven vasospasm by 55% relative to placebo. These findings led to the initiation of the CONSCIOUS trial program to further examine the efficacy and safety of clazosentan in reducing angiographic vasospasm and improving clinical outcome after aneurysmal SAH. In the first of these studies, CONSCIOUS-1, 413 patients were randomized to placebo or clazosentan 1, 5 or 15 mg/h. Clazosentan reduced angiographic vasospasm dose-dependently relative to placebo with a maximum risk reduction of 65% with the highest dose. Despite this, there was no benefit of clazosentan on the secondary protocol-defined morbidity/mortality endpoint; however, additional post-hoc and modified endpoint analyses provided some evidence for a potential clinical benefit. Two additional large-scale studies (CONSCIOUS-2 and CONSCIOUS-3) are now underway to further investigate the potential of clazosentan to improve long-term clinical outcome.

Distribution of radiodense contrast medium after perineural injection of the palmar and palmar metacarpal nerves (low 4-point nerve block): an in vivo and ex vivo study in horses

REASONS FOR PERFORMING STUDY: Evidence-based information is limited on distribution of local anaesthetic solution following perineural analgesia of the palmar (Pa) and palmar metacarpal (PaM) nerves in the distal aspect of the metacarpal (Mc) region ('low 4-point nerve block'). OBJECTIVES: To demonstrate the potential distribution of local anaesthetic solution after a low 4-point nerve block using a radiographic contrast model. METHODS: A radiodense contrast medium was injected subcutaneously over the medial or the lateral Pa nerve at the junction of the proximal three-quarters and distal quarter of the Mc region (Pa injection) and over the ipsilateral PaM nerve immediately distal to the distal aspect of the second or fourth Mc bones (PaM injection) in both forelimbs of 10 mature horses free from lameness. Radiographs were obtained 0, 10 and 20 min after injection and analysed subjectively and objectively. Methylene blue and a radiodense contrast medium were injected in 20 cadaver limbs using the same techniques. Radiographs were obtained and the limbs dissected. RESULTS: After 31/40 (77.5%) Pa injections, the pattern of the contrast medium suggested distribution in the neurovascular bundle. There was significant proximal diffusion with time, but the main contrast medium patch never progressed proximal to the mid-Mc region. The radiological appearance of 2 limbs suggested that contrast medium was present in the digital flexor tendon sheath (DFTS). After PaM injections, the contrast medium was distributed diffusely around the injection site in the majority of the limbs. In cadaver limbs, after Pa injections, the contrast medium and the dye were distributed in the neurovascular bundle in 8/20 (40%) limbs and in the DFTS in 6/20 (30%) of limbs. After PaM injections, the contrast and dye were distributed diffusely around the injection site in 9/20 (45%) limbs and showed diffuse and tubular distribution in 11/20 (55%) limbs. CONCLUSIONS AND POTENTIAL RELEVANCE: Proximal diffusion of local anaesthetic solution after a low 4-point nerve block is unlikely to be responsible for decreasing lameness caused by pain in the proximal Mc region. The DFTS may be penetrated inadvertently when performing a low 4-point nerve block.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Fruit yogurt: any erosive potential regarding teeth?

OBJECTIVE: The capability of drinks and foods to resist pH changes brought about by salivary buffering may play an important role in the dental erosion process in children. The aim of the present study was to test fruit yogurt, a popular snack for children, and the degrees of saturation (pK-pl) with respect to hydroxyapatite and fluorapatite to determine their erosive potential. METHOD AND MATERIALS: A variety of fruit yogurt was tested. To test the pH, 8 readings were taken with a pH electrode for each yogurt. Calcium content was detected by atomic absorption spectrophotometer, phosphorus by the inductively coupled plasma method, and fluoride content by ion chromatography. The degrees of saturation of hydroxyapatite and fluorapatite were calculated by use of a computer program. Statistical analysis was performed using 2-tailed analysis of variance (P < .05) and a post hoc test (Tukey) to determine differences between groups. RESULTS: The pH of each fruit concentrate was significantly different, except for banana yogurt. Except for the phosphorus content of raspberry yogurt, the calcium and phosphorus content for each fruit concentrate were significantly different. Fluoride levels were the same for all yogurts tested, and the degrees of saturation of hydroxyapatite and fluorapatite was positive, indicating supersaturation. CONCLUSION: It could be stated that fruit yogurt has no erosive potential.

High incidence of optic disc swelling at very high altitudes

OBJECTIVES: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers

We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1, 5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions.

Hard thermal loop benchmark for the extraction of the nonperturbative QQ[over ¯] potential

The extraction of the finite temperature heavy quark potential from lattice QCD relies on a spectral analysis of the Wilson loop. General arguments tell us that the lowest lying spectral peak encodes, through its position and shape, the real and imaginary parts of this complex potential. Here we benchmark this extraction strategy using leading order hard-thermal loop (HTL) calculations. In other words, we analytically calculate the Wilson loop and determine the corresponding spectrum. By fitting its lowest lying peak we obtain the real and imaginary parts and confirm that the knowledge of the lowest peak alone is sufficient for obtaining the potential. Access to the full spectrum allows an investigation of spectral features that do not contribute to the potential but can pose a challenge to numerical attempts of an analytic continuation from imaginary time data. Differences in these contributions between the Wilson loop and gauge fixed Wilson line correlators are discussed. To better understand the difficulties in a numerical extraction we deploy the maximum entropy method with extended search space to HTL correlators in Euclidean time and observe how well the known spectral function and values for the real and imaginary parts are reproduced. Possible venues for improvement of the extraction strategy are discussed.