Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infection with hepatitis C virus is one of the main risk factors for HCC. This study analyses the characteristics of the patients with chronic hepatitis C participating in the Swiss Hepatitis C Cohort Study who developed HCC.

Digestive processes in ruminal drinkers characterized by means of the acetaminophen absorption test

The aim of the present study was to measure transit patterns of nutrients and the absorptive ability in ruminal drinkers (RDs) compared with healthy unweaned calves. The acetaminophen (paracetamol) absorption test was used to characterize the oroduodenal transit rate. Clinical examination and the analysis of various blood parameters provided supplementary information on digestive processes. Three unweaned bucket-fed calves (one RD and two healthy controls) each from seven Swiss dairy farms were included in the study. Measurements (tests 1 and 2) were performed twice at an interval of 10 days. Between tests, the feeding technique of the RDs and one control calf per farm was changed to feeding with a nipple instead of by bucket (without nipple). Acetaminophen appearance in the blood was delayed and reduced in RDs compared with the controls. Acid-base metabolism and several haematological and metabolic parameters differed markedly between RDs and healthy controls. The characteristics of the oroduodenal transit rate, absorptive abilities and clinical status in RDs were nearly normalised within 10 days of reconditioning.

Development of a Rasch homogenous short form of the Pathological Narcissism Inventory

During the last decades, the narcissistic personality inventory (npi) was the most widely used questionnaire to measure narcissism as a personality trait. But the npi assesses grandiose narcissism only, while recent discussions emphasize the existence of vulnerable narcissism. The pathological narcissism inventory (pni, pincus et al., 2009) is a new questionnaire assessing these different aspects of narcissism. However, with 54 items on seven subscales, the pni is quite long to serve as a screening tool for narcissistic traits. We therefore developed a short form to facilitate its application in research and practice. Even though the pni covers different symptoms of narcissism, they are all expressions of the same underlying construct. We therefore used the rasch model to guide the item selection. Method and results: a sample of 1837 participants (67.5% female, mean age 26.8 years) was used to choose the items for the short form. Two criteria were adopted: all aspects, represented by the seven subscales in the original, should be retained, and items should be rasch homogenous. In a step-by-step procedure we excluded items successively until reaching a homogenous pool of 22 items. All remaining items had satisfactory fit indices and fitstatistics for the model were good. characteristics of the resulting short form were tested using a new independent validation sample (n=104, mean age = 32.8, 45% female). Correlations of the short pni with different validation measures were comparable to the correlations obtained with the original form, indicating that the two forms were equivalent. Conclusion: the resulting one-dimensional measure can be used as a screening questionnaire for pathological narcissism. The rasch homogeneity facilitates the comparison of narcissism scores among a variety of samples.

Middle and Late Pleistocene humid periods recorded in palaeolake deposits of the Nafud desert, Saudi Arabia

Present climate in the Nafud desert of northern Saudi Arabia is hyper-arid and moisture brought by north-westerly winds scarcely reaches the region. The existence of abundant palaeolake sediments provides evidence for a considerably wetter climate in the past. However, the existing chronological framework of these deposits is solely based on radiocarbon dating of questionable reliability, due to potential post-depositional contamination with younger 14C. By using luminescence dating, we show that the lake deposits were not formed between 40 and 20 ka as suggested previously, but approximately ca 410 ka, 320 ka, 200 ka, 125 ka, and 100 ka ago. All of these humid phases are in good agreement with those recorded in lake sediments and speleothems from southern Arabia. Surprisingly, no Holocene lake deposits were identified. Geological characteristics of the deposits and diatom analysis suggest that a single, perennial lake covered the entire south-western Nafud ca 320 ka ago. In contrast, lakes of the 200 ka, 125 ka, and 100 ka humid intervals were smaller and restricted to interdune depressions of a pre-existing dune relief. The concurrent occurrence of humid phases in the Nafud, southern Arabia and the eastern Mediterranean suggests that moisture in northern Arabia originated either from the Mediterranean due to more frequent frontal depression systems or from stronger Indian monsoon circulation, respectively. However, based on previously published climate model simulations and palaecolimate evidence from central Arabia and the Negev desert, we argue that humid climate conditions in the Nafud were probably caused by a stronger African monsoon and a distinct change in zonal atmospheric circulation.

Status of the Zimmerwald SLR station

The Zimmerwald SLR station is operated in a monostatic mode with 532nm laser pulses emitted at adjustable frequencies of 90-110Hz with energies slightly less than 10mJ. A rotating shutter protects the CSPAD receiver from the backscatter of the transmit beam. These systems are located below the telescope in an operator room housed within the observatory building with the laser system located in a separated, air-conditioned part of the room. All hardware components may be automatically accessed by the control software and from remote if required. Thanks to the fully automatic and remotely controllable SLR operations, the Zimmerwald station is one of the most productive stations in the ILRS network. Key characteristics of the hardware are shown. Specialities like the tracking of the full GLONASS constellation, one-way ranging to the Lunar Reconnaissance Orbiter, and photon reception from bi-static experiments with the Graz SLR station are highlighted as well.

A Lagrangian Analysis of the Northern Hemisphere Subtropical Jet

This study presents a 5-yr climatology of 7-day back trajectories started from the Northern Hemisphere subtropical jet. These trajectories provide insight into the seasonally and regionally varying angular momentum and potential vorticity characteristics of the air parcels that end up in the subtropical jet. The trajectories reveal preferred pathways of the air parcels that reach the subtropical jet from the tropics and the extratropics and allow estimation of the tropical and extratropical forcing of the subtropical jet. The back trajectories were calculated 7 days back in time and started every 6 h from December 2005 to November 2010 using the Interim European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-Interim) dataset as a basis. The trajectories were started from the 345-K isentrope in areas where the wind speed exceeded a seasonally varying threshold and where the wind shear was confined to upper levels. During winter, the South American continent, the Indian Ocean, and the Maritime Continent are preferred areas of ascent into the upper troposphere. From these areas, air parcels follow an anticyclonic pathway into the subtropical jet. During summer, the majority of air parcels ascend over the Himalayas and Southeast Asia. Angular momentum is overall well conserved for trajectories that reach the subtropical jet from the deep tropics. In winter and spring, the hemispheric-mean angular momentum loss amounts to approximately 6%; in summer, it amounts to approximately 18%; and in fall, it amounts to approximately 13%. This seasonal variability is confirmed using an independent potential vorticity–based method to estimate tropical and extratropical forcing of the subtropical jet.

Experimental, theoretical and numerical investigation of the nonlinear micromechanical properties of bone

Aging societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the bone hierarchical organization. A good understanding has been reached for elastic properties on several length scales, but up to now there is a lack of reliable postyield data on the lower length scales. In order to be able to describe the behavior of bone at the microscale, an anisotropic elastic-viscoplastic damage model was developed using an eccentric generalized Hill criterion and nonlinear isotropic hardening. The model was implemented as a user subroutine in Abaqus and verified using single element tests. A FE simulation of microindentation in lamellar bone was finally performed show-ing that the new constitutive model can capture the main characteristics of the indentation response of bone. As the generalized Hill criterion is limited to elliptical and cylindrical yield surfaces and the correct shape for bone is not known, a new yield surface was developed that takes any convex quadratic shape. The main advantage is that in the case of material identification the shape of the yield surface does not have to be anticipated but a minimization results in the optimal shape among all convex quadrics. The generality of the formulation was demonstrated by showing its degeneration to classical yield surfaces. Also, existing yield criteria for bone at multiple length scales were converted to the quadric formulation. Then, a computational study to determine the influence of yield surface shape and damage on the in-dentation response of bone using spherical and conical tips was performed. The constitutive model was adapted to the quadric criterion and yield surface shape and critical damage were varied. They were shown to have a major impact on the indentation curves. Their influence on indentation modulus, hardness, their ratio as well as the elastic to total work ratio were found to be very well described by multilinear regressions for both tip shapes. For conical tips, indentation depth was not a significant fac-tor, while for spherical tips damage was insignificant. All inverse methods based on microindentation suffer from a lack of uniqueness of the found material properties in the case of nonlinear material behavior. Therefore, monotonic and cyclic micropillar com-pression tests in a scanning electron microscope allowing a straightforward interpretation comple-mented by microindentation and macroscopic uniaxial compression tests were performed on dry ovine bone to identify modulus, yield stress, plastic deformation, damage accumulation and failure mecha-nisms. While the elastic properties were highly consistent, the postyield deformation and failure mech-anisms differed between the two length scales. A majority of the micropillars showed a ductile behavior with strain hardening until failure by localization in a slip plane, while the macroscopic samples failed in a quasi-brittle fashion with microcracks coalescing into macroscopic failure surfaces. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behavior of bone at the microscale to a quasi-brittle response driven by the growth of preexisting cracks along interfaces or in the vicinity of pores at the macroscale. Subsequently, a study was undertaken to quantify the topological variability of indentations in bone and examine its relationship with mechanical properties. Indentations were performed in dry human and ovine bone in axial and transverse directions and their topography measured by AFM. Statistical shape modeling of the residual imprint allowed to define a mean shape and describe the variability with 21 principal components related to imprint depth, surface curvature and roughness. The indentation profile of bone was highly consistent and free of any pile up. A few of the topological parameters, in particular depth, showed significant correlations to variations in mechanical properties, but the cor-relations were not very strong or consistent. We could thus verify that bone is rather homogeneous in its micromechanical properties and that indentation results are not strongly influenced by small de-viations from the ideal case. As the uniaxial properties measured by micropillar compression are in conflict with the current literature on bone indentation, another dissipative mechanism has to be present. The elastic-viscoplastic damage model was therefore extended to viscoelasticity. The viscoelastic properties were identified from macroscopic experiments, while the quasistatic postelastic properties were extracted from micropillar data. It was found that viscoelasticity governed by macroscale properties has very little influence on the indentation curve and results in a clear underestimation of the creep deformation. Adding viscoplasticity leads to increased creep, but hardness is still highly overestimated. It was possible to obtain a reasonable fit with experimental indentation curves for both Berkovich and spherical indenta-tion when abandoning the assumption of shear strength being governed by an isotropy condition. These results remain to be verified by independent tests probing the micromechanical strength prop-erties in tension and shear. In conclusion, in this thesis several tools were developed to describe the complex behavior of bone on the microscale and experiments were performed to identify its material properties. Micropillar com-pression highlighted a size effect in bone due to the presence of preexisting cracks and pores or inter-faces like cement lines. It was possible to get a reasonable fit between experimental indentation curves using different tips and simulations using the constitutive model and uniaxial properties measured by micropillar compression. Additional experimental work is necessary to identify the exact nature of the size effect and the mechanical role of interfaces in bone. Deciphering the micromechanical behavior of lamellar bone and its evolution with age, disease and treatment and its failure mechanisms on several length scales will help preventing fractures in the elderly in the future.

Kinetics and kinematics of the tölt: effects of rider interaction and shoeing manipulations

Introduction . Compared to most equine horse breeds which are able to walk, trot and canter /gallop, the gait repertoire of the Icelandic horses additionally includes the lateral gait tölt and frequently also the pace. With respect to the tölt gait, special shoeing, saddling and riding techniques have been developed for Icelandic horses in order to enhance its expressiveness and regularity. Toes are left unnaturally long and heavy shoes and paddings, as well as weighted boots are used to enforce the individual gait predisposition. For the same reason, the rider is placed more caudally to the horse's centre of mass as compared to other riding techniques. The biomechanical impact of these methods on the health of the locomotor system has so far never been subject of systematic research. Objectives . The aims of the presented study are (1) to describe the kinetic and kinematic characteristics of the tölt performed on a treadmill, (2) to understand the mechanical consequences of shoeing manipulation (long hooves, weighted boots) on the loading and protraction movement of the limbs, as well as (3) to study the pressure distribution and effects on the gait pattern of 3 different saddle types used for riding Icelandic horses. Materials and methods . Gait analysis was carried out in 13 Icelandic horses at walk and at slow and medium tölting and trotting speeds on a high-speed treadmill instrumented for measuring vertical ground reaction forces as well as temporal and spatial gait variables. Kinematic data of horse, rider and saddle were measured simultaneously. Gait analysis was first carried out with high, long hooves (SH) without and in combination with weighted boots (ad aim (2)). Afterwards, horses were re-shod according to current horseshoeing standards (SN) and gait analysis was repeated (ad aims (1) and (2)). In a second trial, horses were additionally equipped with a pressure sensitive saddle mat and were ridden with a dressage-like saddle (SDres), an Icelandic saddle (Slcel) and a saddle cushion (SCush) in the standard saddle position (ad aim 3). Results and conclusions . Compared to trot at the same speed, tölting horses had a higher stride rate and lower stride impulses. At the tölt loading of the forelimbs was increased in form of higher peak vertical forces (Fzpeak) due to shorter relative stance durations (StDrel). Conversely, in the hindlimbs, longer StDrel resulted in lower Fzpeak. Despite the higher head-neck position at tölt, there was no measurable shift in weight to the hindlimbs. Footfall rhythm was in most horses laterally coupled at the tölt and frequently had a slight fourbeat and a very short suspension phase at trot; underlining the fact that performance of correct gaits in Icelandic horses needs special training. Gait performance as it is currently judged in competition could be improved using a shoeing with SH, resulting in a 21 ± 5 mm longer dorsal hoof wall, but also a weight gain of 273 ± 50 g at the distal limb due to heavier shoeing material. Compared to SN, SH led to a lower stride rate, a longer stride length and a higher, but not wider, forelimb protraction arc, which were also positively associated with speed. At the tölt, the footfall rhythm showed less tendency to lateral couplets and at the trot, the suspension phase was longer. However, on the long term, SH may have negative implications for the health of the palmar structures of the distal foot by increased limb impulses, higher torques at breakover (up to 20%); as well as peak vertical forces at faster speeds. Compared to the shoeing style, the saddle type had less influence on limb forces or movements. The slight weight shift to the rear with SCush and Slcel may be explained by the more caudal position of the rider relative to the horse's back. With SCush, pressure was highest under the cranial part of the saddle, whereas the saddles with trees had more pressure under the caudal area.

A comment on the article “A collinearity diagnosis of the GNSS geocenter determination” by P. Rebischung, Z. Altamimi, and T. Springer

Meindl et al. (Adv Space Res 51(7):1047–1064, 2013) showed that the geocenter z -component estimated from observations of global navigation satellite systems (GNSS) is strongly correlated to a particular parameter of the solar radiation pressure (SRP) model developed by Beutler et al. (Manuscr Geod 19:367–386, 1994). They analyzed the forces caused by SRP and the impact on the satellites’ orbits. The authors achieved their results using perturbation theory and celestial mechanics. Rebischung et al. (J Geod doi:10.1016/j.asr.2012.10.026, 2013) also deal with the geocenter determination with GNSS. The authors carried out a collinearity diagnosis of the associated parameter estimation problem. They conclude “without much exaggerating that current GNSS are insensitive to any component of geocenter motion”. They explain this inability by the high degree of collinearity of the geocenter coordinates mainly with satellite clock corrections. Based on these results and additional experiments, they state that the conclusions drawn by Meindl et al. (Adv Space Res 51(7):1047–1064, 2013) are questionable. We do not agree with these conclusions and present our arguments in this article. In the first part, we review and highlight the main characteristics of the studies performed by Meindl et al. (Adv Space Res 51(7):1047–1064, 2013) to show that the experiments are quite different from those performed by Rebischung et al. (J Geod doi:10.1016/j.asr.2012.10.026,2013) . In the second part, we show that normal equation (NEQ) systems are regular when estimating geocenter coordinates, implying that the covariance matrices associated with the NEQ systems may be used to assess the sensitivity to geocenter coordinates in a standard way. The sensitivity of GNSS to the components of the geocenter is discussed. Finally, we comment on the arguments raised by Rebischung et al. (J Geod doi:10.1016/j.asr.2012.10.026, 2013) against the results of Meindl et al. (Adv Space Res 51(7):1047–1064, 2013).

Modeling episodic fluid-release events in the ductile carbonates of the Glarus thrust

The exposed Glarus thrust displays midcrustal deformation with tens of kilometers of displacement on an ultrathin layer, the principal slip zone (PSZ). Geological observations indicate that this structure resulted from repeated stick-slip events in the presence of highly overpressured fluids. Here we show that the major characteristics of the Glarus thrust movement (localization, periodicity, and evidence of pressurized fluids) can be reconciled by the coupling of two processes, namely, shear heating and fluid release by carbonate decomposition. During this coupling, slow ductile creep deformation raises the temperature through shear heating and ultimately activates the chemical decomposition of carbonates. The subsequent release of highly overpressurized fluids forms and lubricates the PSZ, allowing a ductile fault to move tens of kilometers on millimeter-thick bands in episodic stick-slip events. This model identifies carbonate decomposition as a key process for motion on the Glarus thrust and explains the source of overpressured fluids accessing the PSZ.

Measuring localized viscoelasticity of the vitreous body using intraocular microprobes.

Vitrectomy is a standard ophthalmic procedure to remove the vitreous body from the eye. The biomechanics of the vitreous affects its duration (by changing the removal rate) and the mechanical forces transmitted via the vitreous on the surrounding tissues during the procedure. Biomechanical characterization of the vitreous is essential for optimizing the design and control of instruments that operate within the vitreous for improved precision, safety, and efficacy. The measurements are carried out using a magnetic microprobe inserted into the vitreous, a method known as magnetic microrheology. The location of the probe is tracked by a microscope/camera while magnetic forces are exerted wirelessly by applied magnetic fields. In this work, in vitro artificial vitreous, ex vivo human vitreous and ex vivo porcine vitreous were characterized. In addition, in vivo rabbit measurements were performed using a suturelessly injected probe. Measurements indicate that viscoelasticity parameters of the ex vivo human vitreous are an order of magnitude different from those of the ex vivo porcine vitreous. The in vivo intra-operative measurements show typical viscoelastic behavior of the vitreous with a lower compliance than the ex vivo measurements. The results of the magnetic microrheology measurements were validated with those obtained by a standard atomic force microscopy (AFM) method and in vitro artificial vitreous. This method allows minimally-invasive characterization of localized mechanical properties of the vitreous in vitro, ex vivo, and in vivo. A better understanding of the characteristics of the vitreous can lead to improvements in treatments concerning vitreal manipulation such as vitrectomy.

Differences in published characteristics of GLE60 and their consequences on computed radiation dose rates along selected flight paths

The radiation dose rates at flight altitudes can increase by orders of magnitude for a short time during energetic solar cosmic ray events, so called ground level enhancements (GLEs). Especially at high latitudes and flight altitudes, solar energetic particles superposed on galactic cosmic rays may cause radiation that exceeds the maximum allowed dosage limit for the general public. Therefore the determination of the radiation dose rate during GLEs should be as reliable as possible. Radiation dose rates along flight paths are typically determined by computer models that are based on cosmic ray flux and anisotropy parameters derived from neutron monitor and/or satellite measurements. The characteristics of the GLE on 15 April 2001 (GLE60) were determined and published by various authors. In this work we compare these results and investigate the consequences on the computed radiation dose rates along selected flight paths. In addition, we compare the computed radiation dose rates with measurements that were made during GLE60 on board two transatlantic flights.

Anatomy of the nail unit and the nail biopsy

The nail unit is the largest and a rather complex skin appendage. It is located on the dorsal aspect of the tips of fingers and toes and has important protective and sensory functions. Development begins in utero between weeks 7 and 8 and is fully formed at birth. For its correct development, a great number of signals are necessary. Anatomically, it consists of 4 epithelial components: the matrix that forms the nail plate; the nail bed that firmly attaches the plate to the distal phalanx; the hyponychium that forms a natural barrier at the physiological point of separation of the nail from the bed; and the eponychium that represents the undersurface of the proximal nail fold which is responsible for the formation of the cuticle. The connective tissue components of the matrix and nail bed dermis are located between the corresponding epithelia and the bone of the distal phalanx. Characteristics of the connective tissue include: a morphogenetic potency for the regeneration of their epithelia; the lateral and proximal nail folds form a distally open frame for the growing nail; and the tip of the digit has rich sensible and sensory innervation. The blood supply is provided by the paired volar and dorsal digital arteries. Veins and lymphatic vessels are less well defined. The microscopic anatomy varies from nail subregion to subregion. Several different biopsy techniques are available for the histopathological evaluation of nail alterations.

Doppler Ultrasound Flow Evaluation of the Uterine Arteries Significantly Correlates with Tumor Size in Cervical Cancer Patients.

PURPOSE The aim of this present study was to evaluate the sonographic correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer, in order to establish a new potential marker to monitor treatment response. METHODS This was a retrospective cohort study of 25 patients who underwent a sonographic evaluation of Doppler flow characteristics of the uterine arteries before surgery or radiochemotherapy for early and locally advanced/advanced cervical cancer, respectively, was analyzed. The primary outcome was the correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer. RESULTS Median age was 49 (range 26-85) years, and mean tumor size was 40.8 ± 17 mm. A significant positive correlation was found between tumor diameter and the uterine artery end-diastolic velocity (r = 0.47, p < 0.05) as well as the peak systolic velocity (r = 0.41, p < 0.05). No correlation was found between tumor size and the pulsatility index or resistance index. CONCLUSIONS In cervical cancer, uterine artery velocity parameters are associated with tumor size. This finding could become particularly useful in the follow-up of locally advanced cervical cancer patients undergoing radiochemotherapy or in corroborating the selection of women with more possibility of a high response rate during neoadjuvant chemotherapy before surgery.

Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog

Hair cycle disturbances are common in dogs and comparable to some alopecic disorders in humans. A normal hair cycle is maintained by follicular stem cells which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the bulge area in humans and dogs, the shared particularity of compound hair follicles as well as similarities in follicular biomarker expression, the dog is a promising model to study human hair cycle and stem cell disorders. To gain insight into the spatial distribution of follicular keratinocytes with stem cell potential in canine compound follicles, we microdissected hair follicles in anagen and telogen from skin samples of freshly euthanized dogs. The keratinocytes isolated from different locations were investigated for their colony forming efficiency, growth and differentiation potential as well as clonal growth. Our results indicate that i) compound and single hair follicles exhibit a comparable spatial distribution pattern with respect to cells with high growth potential and stem cell-like characteristics, ii) the lower isthmus (comprising the bulge) harbors most cells with high growth potential in both, the anagen and the telogen hair cycle stage, iii) unlike in other species, colonies with highest growth potential are rather small with an irregular perimeter and iv) the keratinocytes derived from the bulbar region exhibit characteristics of actively dividing transit amplifying cells. Our results now provide the basis to conduct comparative studies of normal dogs and those with hair cycle disorders with the possibility to extend relevant findings to human patients.