Temperature- and strain-rate-dependent microfabric evolution in monomineralic mylonite: evidence from in situ deformation of norcamphor

Norcamphor (C7H10O) was subjected to plane strain simple shear in a see-through deformation rig at four different strain rate and temperature conditions. Two transient stages in the microfabric evolution to steady state are distinguished. The grain scale mechanisms associated with the microstructural and textural evolution vary with the applied temperature, strain rate and strain. In high-temperature-low-strain-rate experiments, computer integrated polarization microscopy reveals that the texture evolution is closely related to the crystallographic rotation paths and rotation rates of individual grains. High c-axis rotation rates at low to intermediate shear strains are related to the development of a symmetrical c-axis cross girdle by the end of the first transient stage (γ = 1.5 to 2). During the second transient stage (γ = 1.5 to 6), the cross girdle yields to an oblique c-axis single girdle as c-axis rotation rates decrease and the relative activity of grain boundary migration recrystallization increases. Steady state (γ > 8) is characterized by a stable end orientation of the sample texture and the cyclic growth, rotation and consumption of individual grains within the aggregate.

Ultrastructural quantification of cell death after injurious compression of bovine calf articular cartilage

OBJECTIVE: It has been suggested that chondrocyte death by apoptosis may play a role in the pathogenesis of cartilage destruction in osteoarthritis, but the results of in-vivo and in-vitro investigations have been conflicting. To investigate further the cell death in our in-vitro model for traumatic joint injury, we performed a quantitative analysis by electron microscopy (EM) of cell morphology after injurious compression. For comparison, the TUNEL assay was also performed. DESIGN: Articular cartilage explant disks were harvested from newborn calf femoropatellar groove. The disks were subjected to injurious compression (50% strain at a strain rate of 100%/s), incubated for 3 days, and then fixed for quantitative morphological analysis. RESULTS: By TUNEL, the cell apoptosis rate increased from 7 +/- 2% in unloaded controls to 33 +/- 6% after injury (P=0.01; N=8 animals). By EM, the apoptosis rate increased from 5 +/- 1% in unloaded controls to 62 +/- 10% in injured cartilage (P=0.02, N=5 animals). Analysis by EM also identified that of the dead cells in injured disks, 97% were apoptotic by morphology. CONCLUSIONS: These results confirm a significant increase in cell death after injurious compression and suggest that most cell death observed here was by an apoptotic process.

Seismic anisotropy in the Morcles nappe shear zone: Implications for seismic imaging of crustal scale shear zones

Microstructures and textures of calcite mylonites from the Morcles nappe large-scale shear zone in southwestern Switzerland develop principally as a function of 1) extrinsic physical parameters including temperature, stress, strain, strain rate and 2) intrinsic parameters, such as mineral composition. We collected rock samples at a single location from this shear zone, on which laboratory ultrasonic velocities, texture and microstructures were investigated and quantified. The samples had different concentration of secondary mineral phases (< 5 up to 40 vol.%). Measured seismic P wave anisotropy ranges from 6.5% for polyphase mylonites (~ 40 vol.%) to 18.4% in mylonites with < 5 vol.% secondary phases. Texture strength of calcite is the main factor governing the seismic P wave anisotropy. Measured S wave splitting is generally highest in the foliation plane, but its origin is more difficult to explain solely by calcite texture. Additional texture measurements were made on calcite mylonites with low concentration of secondary phases (≤ 10 vol.%) along the metamorphic gradient of the shear zone (15 km distance). A systematic increase in texture strength is observed moving from the frontal part of the shear zone (anchimetamorphism; 280 °C) to the higher temperature, basal part (greenschist facies; 350–400 °C). Calculated P wave velocities become increasingly anisotropic towards the high-strain part of the nappe, from an average of 5.8% in the frontal part to 13.2% in the root of the basal part. Secondary phases raise an additional complexity, and may act either to increase or decrease seismic anisotropy of shear zone mylonites. In light of our findings we reinterpret the origin of some seismically reflective layers in the Grône–Zweisimmen line in southwestern Switzerland (PNR20 Swiss National Research Program). We hypothesize that reflections originate in part from the lateral variation in textural and microstructural arrangement of calcite mylonites in shear zones.

On the initiation of boudinage and folding instabilities in layered elasto-visco-plastic solids - Insights from natural microstructures and numerical simulations

The present understanding of the initiation of boudinage and folding structures is based on viscosity contrasts and stress exponents, considering an intrinsically unstable state of the layer. The criterion of localization is believed to be prescribed by geometry-material interactions, which are often encountered in natural structures. An alternative localization phenomenon has been established for ductile materials, in which instability emerges for critical material parameters and loading rates from homogeneous conditions. In this thesis, conditions are sought under which this type of instability prevails and whether localization in geological materials necessarily requires a trigger by geometric imperfections. The relevance of critical deformation conditions, material parameters and the spatial configuration of instabilities are discussed in a geological context. In order to analyze boudinage geometries, a numerical eigenmode analysis is introduced. This method allows determining natural frequencies and wavelengths of a structure and inducing perturbations on these frequencies. In the subsequent coupled thermo-mechanical simulations, using a grain size evolution and end-member flow laws, localization emerges when material softening through grain size sensitive viscous creep sets in. Pinch-and-swell structures evolve along slip lines through a positive feedback between the matrix response and material bifurcations inside the layer, independent from the mesh-discretization length scale. Since boudinage and folding are considered to express the same general instability, both structures should arise independently of the sign of the loading conditions and for identical material parameters. To this end, the link between material to energy instabilities is approached by means of bifurcation analyses of the field equations and finite element simulations of the coupled system of equations. Boudinage and folding structures develop at the same critical energy threshold, where dissipative work by temperature-sensitive creep overcomes the diffusive capacity of the layer. This finding provides basis for a unified theory for strain localization in layered ductile materials. The numerical simulations are compared to natural pinch-and-swell microstructures, tracing the adaption of grain sizes, textures and creep mechanisms in calcite veins. The switch from dislocation to diffusion creep relates to strain-rate weakening, which is induced by dissipated heat from grain size reduction, and marks the onset of continuous necking. The time-dependent sequence uncovers multiple steady states at different time intervals. Microstructurally and mechanically stable conditions are finally expressed in the pinch-and-swell end members. The major outcome of this study is that boudinage and folding can be described as the same coupled energy-mechanical bifurcation, or as one critical energy attractor. This finding allows the derivation of critical deformation conditions and fundamental material parameters directly from localized structures in the field.

Evolution of mylonitic microfabrics (EMM), a computer application for educational purposes

`Evolution of mylonitic microfabrics' (EMM) is an interactive Filemaker Pro 3.0 application that documents a series of see-through deformation experiments on polycrystalline norcamphor. The application comprises computer animations, graphics and text explanations designed to give students and researchers insight into the interaction and dynamic nature of small-scale, mylonitic processes like intracrystalline glide, dynamic recrystallization and strain localization (microshearing). EMM shows how mylonitic steady state is achieved at different strain rates and temperatures. First, rotational mechanisms like glide-induced vorticity, subgrain rotation recrystallization and rigid-body rotation bring grains' crystal lattices into orientations that are favorable for intracrystalline glide. In a second stage, selective elimination of grains whose lattices are poorly oriented for glide involves grain boundary migration. This strengthens the texture. Temperature and strain rate affect both the relative activity of different strain accommodation mechanisms and the rate of microfabric change. Steady-state microfabrics are characterized by stable texture, grain size and shape-preferred orientations of grains and domains. This involves the cyclical generation and elimination of dynamically recrystallized grains and microshear zones.

Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency

BACKGROUND: Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea metabolism that can lead to hyperammonemic crises and orotic aciduria. To date, a total of 341 causative mutations within the OTC gene have been described. However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed. METHODS: Standard genomic DNA analysis of the OTC gene in five consecutive patients from five families revealed no mutation. Hence, liver tissue was obtained by needle sampling or open biopsy and RNA extracted from liver was analyzed. RESULTS: Complex rearrangements of the OTC transcript (three insertions and two deletions) were found in all five patients. CONCLUSION: In patients with a strong suspicion of OTC deficiency despite normal results of sequencing exonic regions of the OTC gene, characterization of liver OTC mRNA is highly effective in resolving the genotype. Liver tissue sampling by needle aspiration allows for both enzymatic analysis and RNA based diagnostics of OTC deficiency.

Uptake of regular chlamydia testing by U.S. women: a longitudinal study

Background Routine chlamydia screening is a recommended preventive intervention for sexually active women aged ≤25 years in the U.S. but rates of regular uptake are not known. Purpose This study aimed to examine rates of annual chlamydia testing and factors associated with repeat testing in a population of U.S. women. Methods Women aged 15–25 years at any time from January 1, 2002, to December 31, 2006 who were enrolled in 130 commercial health plans were included. Data relating to chlamydia tests were analyzed in 2009. Chlamydia testing rates (per 100 woman-years) by age and rates of repeated annual testing were estimated. Poisson regression was used to examine the effects of age and previous testing on further chlamydia testing within the observation period. Results In total, 2,632,365 women were included. The chlamydia testing rate over the whole study period was 13.6 per 100 woman years after adjusting for age-specific sexual activity; 8.5 (95% CI=6.0, 12.3) per 100 woman-years in those aged 15 years; and 17.7 (95% CI=17.1, 18.9) in those aged 25 years. Among women enrolled for the entire 5-year study period, 25.9% had at least one test but only 0.1% had a chlamydia test every year. Women tested more than once and older women were more likely to be tested again in the observation period. Conclusions The low rates of regular annual chlamydia testing do not comply with national recommendations and would not be expected to have a major impact on the control of chlamydia infection at the population level.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study

Background Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction). Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

Au@Hg nanoalloy formation through direct amalgamation: Structural, spectroscopic, and computational evidence for slow nanoscale diffusion

Dynamic core-shell nanoparticles have received increasing attention in recent years. This paper presents a detailed study of Au-Hg nanoalloys, whose composing elements show a large difference in cohesive energy. A simple method to prepare Au@Hg particles with precise control over the composition up to 15 atom% mercury is introduced, based on reacting a citrate stabilized gold sol with elemental mercury. Transmission electron microscopy shows an increase of particle size with increasing mercury content and, together with X-ray powder diffraction, points towards the presence of a core-shell structure with a gold core surrounded by an Au-Hg solid solution layer. The amalgamation process is described by pseudo-zero-order reaction kinetics, which indicates slow dissolution of mercury in water as the rate determining step, followed by fast scavenging by nanoparticles in solution. Once adsorbed at the surface, slow diffusion of Hg into the particle lattice occurs, to a depth of ca. 3 nm, independent of Hg concentration. Discrete dipole approximation calculations relate the UV-vis spectra to the microscopic details of the nanoalloy structure. Segregation energies and metal distribution in the nanoalloys were modeled by density functional theory calculations. The results indicate slow metal interdiffusion at the nanoscale, which has important implications for synthetic methods aimed at core-shell particles.

Low rate of methicillin-resistant coagulase-positive staphylococcal colonization of veterinary personnel in Hong Kong

Elevated rates of methicillin-resistant Staphylococcus aureus (MRSA) carriage have been reported in veterinary personnel, suggesting an occupational colonization risk. Hong Kong veterinary personnel (n = 150) were sampled for coagulase-positive staphylococci (CPS) nasal colonization. Risk factors for colonization were assessed by questionnaire. Isolates were identified and antibiotic susceptibility determined. All CPS isolates were investigated for mecA carriage, SCCmec type and PVL genes. Two subjects were colonized with methicillin-resistant CPS: one with MRSA (spa type t002 (CC5), SCCmec type II) and one with methicillin-resistant Staphylococcus pseudintermedius (MRSP) (MLST type ST71, SCCmec type II-III). MLST type ST71 S. pseudintermedius strain is the predominant MRSP clone circulating in dogs in Europe and in Hong Kong. The low MR-CPS colonization rate may be associated with low levels of large animal exposure or low rates of MRSA colonization of companion animals in Hong Kong. Colonization with non-aureus CPS, which may cause human infection, must also be considered in veterinary personnel.

Testing the structural and cross-cultural validity of the KIDSCREEN-27 quality of life questionnaire

OBJECTIVES: The aim of this study is to assess the structural and cross-cultural validity of the KIDSCREEN-27 questionnaire. METHODS: The 27-item version of the KIDSCREEN instrument was derived from a longer 52-item version and was administered to young people aged 8-18 years in 13 European countries in a cross-sectional survey. Structural and cross-cultural validity were tested using multitrait multi-item analysis, exploratory and confirmatory factor analysis, and Rasch analyses. Zumbo's logistic regression method was applied to assess differential item functioning (DIF) across countries. Reliability was assessed using Cronbach's alpha. RESULTS: Responses were obtained from n = 22,827 respondents (response rate 68.9%). For the combined sample from all countries, exploratory factor analysis with procrustean rotations revealed a five-factor structure which explained 56.9% of the variance. Confirmatory factor analysis indicated an acceptable model fit (RMSEA = 0.068, CFI = 0.960). The unidimensionality of all dimensions was confirmed (INFIT: 0.81-1.15). Differential item functioning (DIF) results across the 13 countries showed that 5 items presented uniform DIF whereas 10 displayed non-uniform DIF. Reliability was acceptable (Cronbach's alpha = 0.78-0.84 for individual dimensions). CONCLUSIONS: There was substantial evidence for the cross-cultural equivalence of the KIDSCREEN-27 across the countries studied and the factor structure was highly replicable in individual countries. Further research is needed to correct scores based on DIF results. The KIDSCREEN-27 is a new short and promising tool for use in clinical and epidemiological studies.

The functional relationship between yawning and vigilance

BACKGROUND: Although yawning is a ubiquitous and phylogenetically old phenomenon, its origin and purpose remain unclear. The study aimed at testing the widely held hypothesis that yawning is triggered by drowsiness and brings about a reversal or suspension of the process of falling asleep. METHODS: Subjects complaining of excessive sleepiness were spontaneously yawning while trying to stay awake in a quiet and darkened room. Changes in their electroencephalogram (EEG) and heart rate variability (HRV) associated with yawning were compared to changes associated with isolated voluntary body movements. Special care was taken to remove eye blink- and movement-artefacts from the recorded signals. RESULTS: Yawns were preceded and followed by a significantly greater delta activity in EEG than movements (p< or =0.008). After yawning, alpha rhythms were attenuated, decelerated, and shifted towards central brain regions (p< or =0.01), whereas after movements, they were attenuated and accelerated (p<0.02). A significant transient increase of HRV occurred after the onset of yawning and movements, which was followed by a significant slow decrease peaking 17s after onset (p<0.0001). No difference in HRV changes was found between yawns and movements. CONCLUSIONS: Yawning occurred during periods with increased drowsiness and sleep pressure, but was not followed by a measurable increase of the arousal level of the brain. It was neither triggered nor followed by a specific autonomic activation. Our results therefore confirm that yawns occur due to sleepiness, but do not provide evidence for an arousing effect of yawning.

Nanoduct(R) sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis

Determination of chloride concentration in sweat is the current diagnostic gold standard for Cystic Fibrosis (CF). Nanoduct(R) is a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes. The aim of the study was to evaluate the applicability of this system in a clinical setting of three children's hospitals and borderline results were compared with sweat chloride concentration. Over 3 years, 1,041 subjects were tested and in 946 diagnostic results were obtained. In 95 children, Nanoduct(R) failed (9.1% failure rate), mainly due to failures in preterm babies and newborns. Assuming 59 mmol/L as an upper limit of normal conductivity, all our 46 CF patients were correctly diagnosed (sensitivity 100%, 95% CI: 93.1-100; negative predicted value 100% (95% CI: 99.6-100) and only 39 non CF's were false positive (39/900, 4.3%; specificity 95.7%, 95%CI: 94.2-96.9, positive predicted value 54.1% with a 95%CI: 43.4-65.0). Increasing the diagnostic limit to 80 mmol/L, the rate fell to 0.3% (3/900). CF patients had a median conductivity of 115 mmol/L; the non-CF a median of 37 mmol/L. In conclusion, the Nanoduct(R) test is a reliable diagnostic tool for CF diagnosis: It has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion, diagnosis or suspicion of CF. In cases with borderline conductivity (60-80 mmol/L) other additional methods (determination of chloride and genotyping) are indicated.

Sweat testing practice in Swiss hospitals

AIMS: To determine whether the current practice of sweat testing in Swiss hospitals is consistent with the current international guidelines. METHODS: A questionnaire was mailed to all children's hospitals (n = 8), regional paediatric sections of general hospitals (n = 28), and all adult pulmonology centres (n = 8) in Switzerland which care for patients with cystic fibrosis (CF). The results were compared with published "guidelines 2000" of the American National Committee for Clinical Laboratory Standards (NCCLS) and the UK guidelines of 2003. RESULTS: The response rate was 89%. All 8 children's hospitals and 18 out of 23 answering paediatric sections performed sweat tests but none of the adult pulmonology centres. In total, 1560 sweat tests (range: 5-200 tests/centre/year, median 40) per year were done. 88% (23/26) were using Wescor systems, 73% (19/26) the Macroduct system for collecting sweat and 31% (8/26) the Nanoduct system. Sweat chloride was determined by only 62% (16/26) of all centres; of these, only 63% (10/16) indicated to use the recommended diagnostic chloride-CF-reference value of >60 mmol/l. Osmolality was measured in 35%, sodium in 42% and conductivity in 62% of the hospitals. Sweat was collected for maximal 30-120 (median 55) minutes; only three centres used the maximal 30 minutes sample time recommended by the international guidelines. CONCLUSIONS: Sweat testing practice in Swiss hospitals was inconsistent and seldom followed the current international guidelines for sweat collection, analyzing method and reference values. Only 62% were used the chloride concentration as a diagnostic reference, the only accepted diagnostic measurement by the NCCLS or UK guidelines.