Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

BackgroundHepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.MethodsVia questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.ResultsEarly treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 ¿M) and NTBC-levels in the therapeutic range (20¿40 ¿M). Side effects of NTBC are mild and often transient.Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).ConclusionBased on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Time-series analysis of Campylobacter incidence in Switzerland

SUMMARY Campylobacteriosis has been the most common food-associated notifiable infectious disease in Switzerland since 1995. Contact with and ingestion of raw or undercooked broilers are considered the dominant risk factors for infection. In this study, we investigated the temporal relationship between the disease incidence in humans and the prevalence of Campylobacter in broilers in Switzerland from 2008 to 2012. We use a time-series approach to describe the pattern of the disease by incorporating seasonal effects and autocorrelation. The analysis shows that prevalence of Campylobacter in broilers, with a 2-week lag, has a significant impact on disease incidence in humans. Therefore Campylobacter cases in humans can be partly explained by contagion through broiler meat. We also found a strong autoregressive effect in human illness, and a significant increase of illness during Christmas and New Year's holidays. In a final analysis, we corrected for the sampling error of prevalence in broilers and the results gave similar conclusions.

Illegitimate tasks, feelings of resentment, and recovery – longitudinal mediation model

Illegitimate tasks are a relatively new stressor concept, referring to tasks that an employee cannot appropriately expect to carry out. This study tested the hypothesis that illegitimate tasks predicted recovery, mediated by feelings of resentment. The hypothesis was confirmed in a longitudinal study with three waves of measurement.

Localization and Segmentation of 3D Intervertebral Discs in MR Images by Data Driven Estimation

This paper addresses the problem of fully-automatic localization and segmentation of 3D intervertebral discs (IVDs) from MR images. Our method contains two steps, where we first localize the center of each IVD, and then segment IVDs by classifying image pixels around each disc center as foreground (disc) or background. The disc localization is done by estimating the image displacements from a set of randomly sampled 3D image patches to the disc center. The image displacements are estimated by jointly optimizing the training and test displacement values in a data-driven way, where we take into consideration both the training data and the geometric constraint on the test image. After the disc centers are localized, we segment the discs by classifying image pixels around disc centers as background or foreground. The classification is done in a similar data-driven approach as we used for localization, but in this segmentation case we are aiming to estimate the foreground/background probability of each pixel instead of the image displacements. In addition, an extra neighborhood smooth constraint is introduced to enforce the local smoothness of the label field. Our method is validated on 3D T2-weighted turbo spin echo MR images of 35 patients from two different studies. Experiments show that compared to state of the art, our method achieves better or comparable results. Specifically, we achieve for localization a mean error of 1.6-2.0 mm, and for segmentation a mean Dice metric of 85%-88% and a mean surface distance of 1.3-1.4 mm.

How task experience influences students' performance expectancies: The role of certainty

The importance of performance expectancies for predicting behavior has long been highlighted in research on expectancy-value models. These models do not take into account that expectancies may vary in terms of their certainty. The study tested the following predictions: task experience leads to a higher certainty of expectancies; certainty and mean expectancies are empirically distinguishable; and expectancies held with high certainty are more accurate for predicting performance. 273 Grade 8 students reported their performance expectancy and the certainty of expectation with regard to a mathematics examination immediately before and after the examination. Actual grades on the examination were also assessed. The results supported the predictions: there was an increase in certainty between the two times of measurement; expectancies and certainty were unrelated at both times of measurement; and for students initially reporting higher certainty, the accuracy of the performance expectancy (i.e., the relation between expectancy and performance) was higher than for students reporting lower certainty. Given lower certainty, the accuracy increased after the students had experience with the examination. The data indicate that it may be useful to include certainty as an additional variable in expectancy-value models.

Fusion of fundus images and MRI data of the human eye

Purpose Ophthalmologists are confronted with a set of different image modalities to diagnose eye tumors e.g., fundus photography, CT and MRI. However, these images are often complementary and represent pathologies differently. Some aspects of tumors can only be seen in a particular modality. A fusion of modalities would improve the contextual information for diagnosis. The presented work attempts to register color fundus photography with MRI volumes. This would complement the low resolution 3D information in the MRI with high resolution 2D fundus images. Methods MRI volumes were acquired from 12 infants under the age of 5 with unilateral retinoblastoma. The contrast-enhanced T1-FLAIR sequence was performed with an isotropic resolution of less than 0.5mm. Fundus images were acquired with a RetCam camera. For healthy eyes, two landmarks were used: the optic disk and the fovea. The eyes were detected and extracted from the MRI volume using a 3D adaption of the Fast Radial Symmetry Transform (FRST). The cropped volume was automatically segmented using the Split Bregman algorithm. The optic nerve was enhanced by a Frangi vessel filter. By intersection the nerve with the retina the optic disk was found. The fovea position was estimated by constraining the position with the angle between the optic and the visual axis as well as the distance from the optic disk. The optical axis was detected automatically by fitting a parable on to the lens surface. On the fundus, the optic disk and the fovea were detected by using the method of Budai et al. Finally, the image was projected on to the segmented surface using the lens position as the camera center. In tumor affected eyes, the manually segmented tumors were used instead of the optic disk and macula for the registration. Results In all of the 12 MRI volumes that were tested the 24 eyes were found correctly, including healthy and pathological cases. In healthy eyes the optic nerve head was found in all of the tested eyes with an error of 1.08 +/- 0.37mm. A successful registration can be seen in figure 1. Conclusions The presented method is a step toward automatic fusion of modalities in ophthalmology. The combination enhances the MRI volume with higher resolution from the color fundus on the retina. Tumor treatment planning is improved by avoiding critical structures and disease progression monitoring is made easier.

A chrysophyte-based quantitative reconstruction of winter severity from varved lake sediments in NE Poland during the past millennium and its relationship to natural climate variability

Chrysophyte cysts are recognized as powerful proxies of cold-season temperatures. In this paper we use the relationship between chrysophyte assemblages and the number of days below 4 °C (DB4 °C) in the epilimnion of a lake in northern Poland to develop a transfer function and to reconstruct winter severity in Poland for the last millennium. DB4 °C is a climate variable related to the length of the winter. Multivariate ordination techniques were used to study the distribution of chrysophytes from sediment traps of 37 low-land lakes distributed along a variety of environmental and climatic gradients in northern Poland. Of all the environmental variables measured, stepwise variable selection and individual Redundancy analyses (RDA) identified DB4 °C as the most important variable for chrysophytes, explaining a portion of variance independent of variables related to water chemistry (conductivity, chlorides, K, sulfates), which were also important. A quantitative transfer function was created to estimate DB4 °C from sedimentary assemblages using partial least square regression (PLS). The two-component model (PLS-2) had a coefficient of determination of View the MathML sourceRcross2 = 0.58, with root mean squared error of prediction (RMSEP, based on leave-one-out) of 3.41 days. The resulting transfer function was applied to an annually-varved sediment core from Lake Żabińskie, providing a new sub-decadal quantitative reconstruction of DB4 °C with high chronological accuracy for the period AD 1000–2010. During Medieval Times (AD 1180–1440) winters were generally shorter (warmer) except for a decade with very long and severe winters around AD 1260–1270 (following the AD 1258 volcanic eruption). The 16th and 17th centuries and the beginning of the 19th century experienced very long severe winters. Comparison with other European cold-season reconstructions and atmospheric indices for this region indicates that large parts of the winter variability (reconstructed DB4 °C) is due to the interplay between the oscillations of the zonal flow controlled by the North Atlantic Oscillation (NAO) and the influence of continental anticyclonic systems (Siberian High, East Atlantic/Western Russia pattern). Differences with other European records are attributed to geographic climatological differences between Poland and Western Europe (Low Countries, Alps). Striking correspondence between the combined volcanic and solar forcing and the DB4 °C reconstruction prior to the 20th century suggests that winter climate in Poland responds mostly to natural forced variability (volcanic and solar) and the influence of unforced variability is low.

The deglaciation history of the Simplon region (southern Swiss Alps) constrained by 10Be exposure dating of ice-molded bedrock surfaces

The deglaciation history of the Swiss Alps after the Last Glacial Maximum involved the decay of several ice domes and the subsequent disintegration of valley glaciers at high altitude. Here we use bedrock exposure dating to reconstruct the temporal and spatial pattern of ice retreat at the Simplon Pass (altitude: ∼2000 m) located 40 km southwest of the ‘Rhône ice dome’. Eleven 10Be exposure ages from glacially polished quartz veins and ice-molded bedrock surfaces cluster tightly between 13.5 ± 0.6 ka and 15.4 ± 0.6 ka (internal errors) indicating that the Simplon Pass depression became ice-free at 14.1 ± 0.4 ka (external error of mean age). This age constraint is interpreted to record the melting of the high valley glaciers in the Simplon Pass region during the warm Bølling–Allerød interstadial shortly after the Oldest Dryas stadial. Two bedrock samples collected a few hundred meters above the pass depression yield older 10Be ages of 17.8 ± 0.6 ka and 18.0 ± 0.6 ka. These ages likely reflect the initial downwasting of the Rhône ice dome and the termination of the ice transfluence from the ice dome across the Simplon Pass toward the southern foreland. There, the retreat of the piedmont glacier in Val d’Ossola was roughly synchronous with the decay of the Rhône ice dome in the interior of the mountain belt, as shown by 10Be ages of 17.7 ± 0.9 ka and 16.1 ± 0.6 ka for a whaleback at ∼500 m elevation near Montecrestese in northern Italy. In combination with well-dated paleoclimate records derived from lake sediments, our new age data suggest that during the deglaciation of the European Alps the decay of ice domes was approximately synchronous with the retreat of piedmont glaciers in the foreland and was followed by the melting of high-altitude valley glaciers after the transition from the Oldest Dryas to the Bølling–Allerød, when mean annual temperatures rose rapidly by ∼3 °C.

Brief Communication: "An inventory of permafrost evidence for the European Alps"

The investigation and modelling of permafrost distribution, particularly in areas of discontinuous permafrost, is challenging due to spatial heterogeneity, remoteness of measurement sites and data scarcity. We have designed a strategy for standardizing different local data sets containing evidence of the presence or absence of permafrost into an inventory for the entire European Alps. With this brief communication, we present the structure and contents of this inventory. This collection of permafrost evidence not only highlights existing data and allows new analyses based on larger data sets, but also provides complementary information for an improved interpretation of monitoring results.

Quantification of water content across a cement-clay interface using high resolution neutron radiography

In many designs for radioactive waste repositories, cement and clay will come into direct contact. The geochemical contrast between cement and clay will lead to mass fluxes across the interface, which consequently results in alteration of structural and transport properties of both materials that may affect the performance of the multi-barrier system. We present an experimental approach to study cement-clay interactions with a cell to accommodate small samples of cement and clay. The cell design allows both in situ measurement of water content across the sample using neutron radiography and measurement of transport parameters using through-diffusion tracer experiments. The aim of the high- resolution neutron radiography experiments was to monitor changes in water content (porosity) and their spatial extent. Neutron radiographs of several evolving cement-clay interfaces delivered quantitative data which allow resolving local water contents within the sample domain. In the present work we explored the uncertainties of the derived water contents with regard to various input parameters and with regard to the applied image correction procedures. Temporal variation of measurement conditions created absolute uncertainty of the water content in the order of ±0.1 (m3/m3), which could not be fully accounted for by correction procedures. Smaller relative changes in water content between two images can be derived by specific calibrations to two sample regions with different, invariant water contents.

Body Height Estimation from Femur Measurements in Postmortem Computed Tomography

After attending this presentation, attendees will: (1) understand how body height from computed tomography data can be estimated; and, (2) gain knowledge about the accuracy of estimated body height and limitations. The presentation will impact the forensic science community by providing knowledge and competence which will enable attendees to develop formulas for single bones to reconstruct body height using postmortem Computer Tomography (p-CT) data. The estimation of Body Height (BH) is an important component of the identification of corpses and skeletal remains. Stature can be estimated with relative accuracy via the measurement of long bones, such as the femora. Compared to time-consuming maceration procedures, p-CT allows fast and simple measurements of bones. This study undertook four objectives concerning the accuracy of BH estimation via p-CT: (1) accuracy between measurements on native bone and p-CT imaged bone (F1 according to Martin 1914); (2) intra-observer p-CT measurement precision; (3) accuracy between formula-based estimation of the BH and conventional body length measurement during autopsy; and, (4) accuracy of different estimation formulas available.1 In the first step, the accuracy of measurements in the CT compared to those obtained using an osteometric board was evaluated on the basis of eight defleshed femora. Then the femora of 83 female and 144 male corpses of a Swiss population for which p-CTs had been performed, were measured at the Institute of Forensic Medicine in Bern. After two months, 20 individuals were measured again in order to assess the intraobserver error. The mean age of the men was 53±17 years and that of the women was 61±20 years. Additionally, the body length of the corpses was measured conventionally. The mean body length was 176.6±7.2cm for men and 163.6±7.8cm for women. The images that were obtained using a six-slice CT were reconstructed with a slice thickness of 1.25mm. Analysis and measurements of CT images were performed on a multipurpose workstation. As a forensic standard procedure, stature was estimated by means of the regression equations by Penning & Riepert developed on a Southern German population and for comparison, also those referenced by Trotter & Gleser “American White.”2,3 All statistical tests were performed with a statistical software. No significant differences were found between the CT and osteometric board measurements. The double p-CT measurement of 20 individuals resulted in an absolute intra-observer difference of 0.4±0.3mm. For both sexes, the correlation between the body length and the estimated BH using the F1 measurements was highly significant. The correlation coefficient was slightly higher for women. The differences in accuracy of the different formulas were small. While the errors of BH estimation were generally ±4.5–5.0cm, the consideration of age led to an increase in accuracy of a few millimetres to about 1cm. BH estimations according to Penning & Riepert and Trotter & Gleser were slightly more accurate when age-at-death was taken into account.2,3 That way, stature estimations in the group of individuals older than 60 years were improved by about 2.4cm and 3.1cm.2,3 The error of estimation is therefore about a third of the common ±4.7cm error range. Femur measurements in p-CT allow very accurate BH estimations. Estimations according to Penning led to good results that (barely) come closer to the true value than the frequently used formulas by Trotter & Gleser “American White.”2,3 Therefore, the formulas by Penning & Riepert are also validated for this substantial recent Swiss population.

Quantum Nondemolition Measurement Enables Macroscopic Leggett-Garg Tests

We show how a test of macroscopic realism based on Leggett-Garg inequalities (LGIs) can be performed in a macroscopic system. Using a continuous-variable approach, we consider quantum nondemolition (QND) measurements applied to atomic ensembles undergoing magnetically driven coherent oscillation. We identify measurement schemes requiring only Gaussian states as inputs and giving a significant LGI violation with realistic experimental parameters and imperfections. The predicted violation is shown to be due to true quantum effects rather than to a classical invasivity of the measurement. Using QND measurements to tighten the “clumsiness loophole” forces the stubborn macrorealist to recreate quantum backaction in his or her account of measurement.

Prediction of Trabecular Bone Anisotropy from Quantitative Computed Tomography using Supervised Learning and a Novel Morphometric Feature Descriptor

Patient-specific biomechanical models including local bone mineral density and anisotropy have gained importance for assessing musculoskeletal disorders. However the trabecular bone anisotropy captured by high-resolution imaging is only available at the peripheral skeleton in clinical practice. In this work, we propose a supervised learning approach to predict trabecular bone anisotropy that builds on a novel set of pose invariant feature descriptors. The statistical relationship between trabecular bone anisotropy and feature descriptors were learned from a database of pairs of high resolution QCT and clinical QCT reconstructions. On a set of leave-one-out experiments, we compared the accuracy of the proposed approach to previous ones, and report a mean prediction error of 6% for the tensor norm, 6% for the degree of anisotropy and 19◦ for the principal tensor direction. These findings show the potential of the proposed approach to predict trabecular bone anisotropy from clinically available QCT images.

Biomechanical Role of Bone Anisotropy Estimated on Clinical CT Scans by Image Registration

Image-based modeling is a popular approach to perform patient-specific biomechanical simulations. Accurate modeling is critical for orthopedic application to evaluate implant design and surgical planning. It has been shown that bone strength can be estimated from the bone mineral density (BMD) and trabecular bone architecture. However, these findings cannot be directly and fully transferred to patient-specific modeling since only BMD can be derived from clinical CT. Therefore, the objective of this study was to propose a method to predict the trabecular bone structure using a µCT atlas and an image registration technique. The approach has been evaluated on femurs and patellae under physiological loading. The displacement and ultimate force for femurs loaded in stance position were predicted with an error of 2.5% and 3.7%, respectively, while predictions obtained with an isotropic material resulted in errors of 7.3% and 6.9%. Similar results were obtained for the patella, where the strain predicted using the registration approach resulted in an improved mean squared error compared to the isotropic model. We conclude that the registration of anisotropic information from of a single template bone enables more accurate patient-specific simulations from clinical image datasets than isotropic model.

Periacetabular osteotomy restores the typically excessive range of motion in dysplastic hips with a spherical head

BACKGROUND Residual acetabular dysplasia is seen in combination with femoral pathomorphologies including an aspherical femoral head and valgus neck-shaft angle with high antetorsion. It is unclear how these femoral pathomorphologies affect range of motion (ROM) and impingement zones after periacetabular osteotomy. QUESTIONS/PURPOSES (1) Does periacetabular osteotomy (PAO) restore the typically excessive ROM in dysplastic hips compared with normal hips; (2) how do impingement locations differ in dysplastic hips before and after PAO compared with normal hips; (3) does a concomitant cam-type morphology adversely affect internal rotation; and (4) does a concomitant varus-derotation intertrochanteric osteotomy (IO) affect external rotation? METHODS Between January 1999 and March 2002, we performed 200 PAOs for dysplasia; of those, 27 hips (14%) met prespecified study inclusion criteria, including availability of a pre- and postoperative CT scan that included the hip and the distal femur. In general, we obtained those scans to evaluate the pre- and postoperative acetabular and femoral morphology, the degree of acetabular reorientation, and healing of the osteotomies. Three-dimensional surface models based on CT scans of 27 hips before and after PAO and 19 normal hips were created. Normal hips were obtained from a population of CT-based computer-assisted THAs using the contralateral hip after exclusion of symptomatic hips or hips with abnormal radiographic anatomy. Using validated and computerized methods, we then determined ROM (flexion/extension, internal- [IR]/external rotation [ER], adduction/abduction) and two motion patterns including the anterior (IR in flexion) and posterior (ER in extension) impingement tests. The computed impingement locations were assigned to anatomical locations of the pelvis and the femur. ROM was calculated separately for hips with (n = 13) and without (n = 14) a cam-type morphology and PAOs with (n = 9) and without (n = 18) a concomitant IO. A post hoc power analysis based on the primary research question with an alpha of 0.05 and a beta error of 0.20 revealed a minimal detectable difference of 4.6° of flexion. RESULTS After PAO, flexion, IR, and adduction/abduction did not differ from the nondysplastic control hips with the numbers available (p ranging from 0.061 to 0.867). Extension was decreased (19° ± 15°; range, -18° to 30° versus 28° ± 3°; range, 19°-30°; p = 0.017) and ER in 0° flexion was increased (25° ± 18°; range, -10° to 41° versus 38° ± 7°; range, 17°-41°; p = 0.002). Dysplastic hips had a higher prevalence of extraarticular impingement at the anteroinferior iliac spine compared with normal hips (48% [13 of 27 hips] versus 5% [one of 19 hips], p = 0.002). A PAO increased the prevalence of impingement for the femoral head from 30% (eight of 27 hips) preoperatively to 59% (16 of 27 hips) postoperatively (p = 0.027). IR in flexion was decreased in hips with a cam-type deformity compared with those with a spherical femoral head (p values from 0.002 to 0.047 for 95°-120° of flexion). A concomitant IO led to a normalization of ER in extension (eg, 37° ± 7° [range, 21°-41°] of ER in 0° of flexion in hips with concomitant IO compared with 38° ± 7° [range, 17°-41°] in nondysplastic control hips; p = 0.777). CONCLUSIONS Using computer simulation of hip ROM, we could show that the PAO has the potential to restore the typically excessive ROM in dysplastic hips. However, a PAO can increase the prevalence of secondary intraarticular impingement of the aspherical femoral head and extraarticular impingement of the anteroinferior iliac spines in flexion and internal rotation. A cam-type morphology can result in anterior impingement with restriction of IR. Additionally, a valgus hip with high antetorsion can result in posterior impingement with decreased ER in extension, which can be normalized with a varus derotation IO of the femur. However, indication of an additional IO needs to be weighed against its inherent morbidity and possible complications. The results are based on a limited number of hips with a pre- and postoperative CT scan after PAO. Future prospective studies are needed to verify the current results based on computer simulation and to test their clinical importance.