Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

PURPOSE: In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS: A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS: Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. CONCLUSIONS: The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis

Background Adolescent Idiopathic Scoliosis is the most common type of spinal deformity, and whilst the risk of progression appears to be biomechanically mediated (larger deformities are more likely to progress), the detailed biomechanical mechanisms driving progression are not well understood. Gravitational forces in the upright position are the primary sustained loads experienced by the spine. In scoliosis they are asymmetrical, generating moments about the spinal joints which may promote asymmetrical growth and deformity progression. Using 3D imaging modalities to estimate segmental torso masses allows the gravitational loading on the scoliotic spine to be determined. The resulting distribution of joint moments aids understanding of the mechanics of scoliosis progression. Methods Existing low-dose CT scans were used to estimate torso segment masses and joint moments for 20 female scoliosis patients. Intervertebral joint moments at each vertebral level were found by summing the moments of each of the torso segment masses above the required joint. Results The patients’ mean age was 15.3 years (SD 2.3; range 11.9 – 22.3 years); mean thoracic major Cobb angle 52° (SD 5.9°; range 42°-63°) and mean weight 57.5 kg (SD 11.5 kg; range 41 – 84.7 kg). Joint moments of up to 7 Nm were estimated at the apical level. No significant correlation was found between the patients’ major Cobb angles and apical joint moments. Conclusions Patients with larger Cobb angles do not necessarily have higher joint moments, and curve shape is an important determinant of joint moment distribution. These findings may help to explain the variations in progression between individual patients. This study suggests that substantial corrective forces are required of either internal instrumentation or orthoses to effectively counter the gravity-induced moments acting to deform the spinal joints of idiopathic scoliosis patients.

Stochastic model for simulating maize yield

Maize is one of the most important crops in the world. The products generated from this crop are largely used in the starch industry, the animal and human nutrition sector, and biomass energy production and refineries. For these reasons, there is much interest in figuring the potential grain yield of maize genotypes in relation to the environment in which they will be grown, as the productivity directly affects agribusiness or farm profitability. Questions like these can be investigated with ecophysiological crop models, which can be organized according to different philosophies and structures. The main objective of this work is to conceptualize a stochastic model for predicting maize grain yield and productivity under different conditions of water supply while considering the uncertainties of daily climate data. Therefore, one focus is to explain the model construction in detail, and the other is to present some results in light of the philosophy adopted. A deterministic model was built as the basis for the stochastic model. The former performed well in terms of the curve shape of the above-ground dry matter over time as well as the grain yield under full and moderate water deficit conditions. Through the use of a triangular distribution for the harvest index and a bivariate normal distribution of the averaged daily solar radiation and air temperature, the stochastic model satisfactorily simulated grain productivity, i.e., it was found that 10,604 kg ha(-1) is the most likely grain productivity, very similar to the productivity simulated by the deterministic model and for the real conditions based on a field experiment. © 2012 American Society of Agricultural and Biological Engineers.

Yield losses in grain sorghum due to rust infection

Although rust (caused by Puccinia purpurea) is a common disease in Australian grain sorghum crops, particularly late in the growing season (April onwards), its potential to reduce yield has not been quantified. Field trials were conducted in Queensland between 2003 and 2005 to evaluate the effect of sorghum rust on grain yield of two susceptible sorghum hybrids (Tx610 and Pride). Rust was managed from 28-35 days after sowing until physiological maturity by applying oxycarboxin (1 kg active ingredient/100 L of water/ha) every 10 days. When data were combined for the hybrids, yield losses ranged from 13.1% in 2005 to 3.2% in 2003 but differences in yield the between sprayed and unsprayed treatments were statistically significant (P a parts per thousand currency signaEuro parts per thousand 0.05) only in 2005. Final area under the disease progress curve (AUDPC) values reflected the yield losses in each year. The higher yield loss in 2005 can be attributed primarily to the early development of the rust epidemic and the higher inoculum levels in spreader plots at the time of planting of the trials.

Step based physical activity guidelines for preschool-aged children

OBJECTIVE Public health organizations recommend that preschool-aged children accumulate at least 3h of physical activity (PA) daily. Objective monitoring using pedometers offers an opportunity to measure preschooler's PA and assess compliance with this recommendation. The purpose of this study was to derive step-based recommendations consistent with the 3h PA recommendation for preschool-aged children. METHOD The study sample comprised 916 preschool-aged children, aged 3 to 6years (mean age=5.0+/-0.8years). Children were recruited from kindergartens located in Portugal, between 2009 and 2013. Children wore an ActiGraph GT1M accelerometer that measured PA intensity and steps per day simultaneously over a 7-day monitoring period. Receiver operating characteristic (ROC) curve analysis was used to identify the daily step count threshold associated with meeting the daily 3hour PA recommendation. RESULTS A significant correlation was observed between minutes of total PA and steps per day (r=0.76, p<0.001). The optimal step count for >/=3h of total PA was 9099 steps per day (sensitivity (90%) and specificity (66%)) with area under the ROC curve=0.86 (95% CI: 0.84 to 0.88). CONCLUSION Preschool-aged children who accumulate less than 9000 steps per day may be considered Insufficiently Active.

ac susceptibility and electrical resistivity in Fe80-xNixCr20 (21 \leq x \leq 30) alloys

ac susceptibility and electrical resistivity studies on polycrystalline Fe80-xNixCr20 (21 \leq x \leq 30) alloys, with x=21, 23, 26, and 30, between 4.2 and 80 K, are reported. A previous dc magnetization study indicated the presence of ferro-spin-glass mixed-phase behavior in x=23 and 26 alloys while the alloys with x=21 and 30 were found to be spin-glass and ferromagnetic, respectively. The present ac susceptibility results support the above picture. In the electrical resistivity study, a low-temperature minimum in the resistivity-temperature curve is observed in all the alloys except the ferromagnetic one.

Quality of ALICE SSD modules revealed by electrical tests

ALICE (A Large Ion Collider Experiment) is an experiment at CERN (European Organization for Nuclear Research), where a heavy-ion detector is dedicated to exploit the unique physics potential of nucleus-nucleus interactions at LHC (Large Hadron Collider) energies. In a part of that project, 716 so-called type V4 modules were assembles in Detector Laboratory of Helsinki Institute of Physics during the years 2004 - 2006. Altogether over a million detector strips has made this project the most massive particle detector project in the science history of Finland. One ALICE SSD module consists of a double-sided silicon sensor, two hybrids containing 12 HAL25 front end readout chips and some passive components, such has resistors and capacitors. The components are connected together by TAB (Tape Automated Bonding) microcables. The components of the modules were tested in every assembly phase with comparable electrical tests to ensure the reliable functioning of the detectors and to plot the possible problems. The components were accepted or rejected by the limits confirmed by ALICE collaboration. This study is concentrating on the test results of framed chips, hybrids and modules. The total yield of the framed chips is 90.8%, hybrids 96.1% and modules 86.2%. The individual test results have been investigated in the light of the known error sources that appeared during the project. After solving the problems appearing during the learning-curve of the project, the material problems, such as defected chip cables and sensors, seemed to induce the most of the assembly rejections. The problems were typically seen in tests as too many individual channel failures. Instead, the bonding failures rarely caused the rejections of any component. One sensor type among three different sensor manufacturers has proven to have lower quality than the others. The sensors of this manufacturer are very noisy and their depletion voltage are usually outside of the specification given to the manufacturers. Reaching 95% assembling yield during the module production demonstrates that the assembly process has been highly successful.

Prediction of masonry compressive behaviour using a damage mechanics inspired modelling method

Masonry under compression is affected by the properties of its constituents and their interfaces. In spite of extensive investigations of the behaviour of masonry under compression, the information in the literature cannot be regarded as comprehensive due to ongoing inventions of new generation products – for example, polymer modified thin layer mortared masonry and drystack masonry. As comprehensive experimental studies are very expensive, an analytical model inspired by damage mechanics is developed and applied to the prediction of the compressive behaviour of masonry in this paper. The model incorporates a parabolic progressively softening stress-strain curve for the units and a progressively stiffening stress-strain curve until a threshold strain for the combined mortar and the unit-mortar interfaces is reached. The model simulates the mutual constraints imposed by each of these constituents through their respective tensile and compressive behaviour and volumetric changes. The advantage of the model is that it requires only the properties of the constituents and considers masonry as a continuum and computes the average properties of the composite masonry prisms/wallettes; it does not require discretisation of prism or wallette similar to the finite element methods. The capability of the model in capturing the phenomenological behaviour of masonry with appropriate elastic response, stiffness degradation and post peak softening is presented through numerical examples. The fitting of the experimental data to the model parameters is demonstrated through calibration of some selected test data on units and mortar from the literature; the calibrated model is shown to predict the responses of the experimentally determined masonry built using the corresponding units and mortar quite well. Through a series of sensitivity studies, the model is also shown to predict the masonry strength appropriately for changes to the properties of the units and mortar, the mortar joint thickness and the ratio of the height of unit to mortar joint thickness. The unit strength is shown to affect the masonry strength significantly. Although the mortar strength has only a marginal effect, reduction in mortar joint thickness is shown to have a profound effect on the masonry strength. The results obtained from the model are compared with the various provisions in the Australian Masonry Structures Standard AS3700 (2011) and Eurocode 6.

Boundedness of weakly singular integral operators on domains

The monograph dissertation deals with kernel integral operators and their mapping properties on Euclidean domains. The associated kernels are weakly singular and examples of such are given by Green functions of certain elliptic partial differential equations. It is well known that mapping properties of the corresponding Green operators can be used to deduce a priori estimates for the solutions of these equations. In the dissertation, natural size- and cancellation conditions are quantified for kernels defined in domains. These kernels induce integral operators which are then composed with any partial differential operator of prescribed order, depending on the size of the kernel. The main object of study in this dissertation being the boundedness properties of such compositions, the main result is the characterization of their Lp-boundedness on suitably regular domains. In case the aforementioned kernels are defined in the whole Euclidean space, their partial derivatives of prescribed order turn out to be so called standard kernels that arise in connection with singular integral operators. The Lp-boundedness of singular integrals is characterized by the T1 theorem, which is originally due to David and Journé and was published in 1984 (Ann. of Math. 120). The main result in the dissertation can be interpreted as a T1 theorem for weakly singular integral operators. The dissertation deals also with special convolution type weakly singular integral operators that are defined on Euclidean spaces.

On Random Planar Curves and Their Scaling Limits

Planar curves arise naturally as interfaces between two regions of the plane. An important part of statistical physics is the study of lattice models. This thesis is about the interfaces of 2D lattice models. The scaling limit is an infinite system limit which is taken by letting the lattice mesh decrease to zero. At criticality, the scaling limit of an interface is one of the SLE curves (Schramm-Loewner evolution), introduced by Oded Schramm. This family of random curves is parametrized by a real variable, which determines the universality class of the model. The first and the second paper of this thesis study properties of SLEs. They contain two different methods to study the whole SLE curve, which is, in fact, the most interesting object from the statistical physics point of view. These methods are applied to study two symmetries of SLE: reversibility and duality. The first paper uses an algebraic method and a representation of the Virasoro algebra to find common martingales to different processes, and that way, to confirm the symmetries for polynomial expected values of natural SLE data. In the second paper, a recursion is obtained for the same kind of expected values. The recursion is based on stationarity of the law of the whole SLE curve under a SLE induced flow. The third paper deals with one of the most central questions of the field and provides a framework of estimates for describing 2D scaling limits by SLE curves. In particular, it is shown that a weak estimate on the probability of an annulus crossing implies that a random curve arising from a statistical physics model will have scaling limits and those will be well-described by Loewner evolutions with random driving forces.

Jumping numbers of a simple complete ideal in a two-dimensional regular local ring

The multiplier ideals of an ideal in a regular local ring form a family of ideals parametrized by non-negative rational numbers. As the rational number increases the corresponding multiplier ideal remains unchanged until at some point it gets strictly smaller. A rational number where this kind of diminishing occurs is called a jumping number of the ideal. In this manuscript we shall give an explicit formula for the jumping numbers of a simple complete ideal in a two dimensional regular local ring. In particular, we obtain a formula for the jumping numbers of an analytically irreducible plane curve. We then show that the jumping numbers determine the equisingularity class of the curve.

Numerical computation of the module of a quadrilateral

The module of a quadrilateral is a positive real number which divides quadrilaterals into conformal equivalence classes. This is an introductory text to the module of a quadrilateral with some historical background and some numerical aspects. This work discusses the following topics: 1. Preliminaries 2. The module of a quadrilateral 3. The Schwarz-Christoffel Mapping 4. Symmetry properties of the module 5. Computational results 6. Other numerical methods Appendices include: Numerical evaluation of the elliptic integrals of the first kind. Matlab programs and scripts and possible topics for future research. Numerical results section covers additive quadrilaterals and the module of a quadrilateral under the movement of one of its vertex.

Application of ultraspherical polynomials to forced oscillations of a third-order non-linear system

In this paper the method of ultraspherical polynomial approximation is applied to study the steady-state response in forced oscillations of a third-order non-linear system. The non-linear function is expanded in ultraspherical polynomials and the expansion is restricted to the linear term. The equation for the response curve is obtained by using the linearized equation and the results are presented graphically. The agreement between the approximate solution and the analog computer solution is satisfactory. The problem of stability is not dealt with in this paper.

Mechanism of glycine uptake by the silk glands of the silkworm Bombyx mori L

The transport of glycine in vitro into the silk glands of the silkworm has been studied. Glycine accumulates inside the tissue to a concentration higher than that present outside, indicating an active transport mechanism. The kinetics of uptake show a biphasic curve and two apparent Km values for accumulation, 0.33 mM and 5.00 mM. The effect of inhibitors on the energy metabolism of glycine transport is inconclusive. Exchange studies indicate the existence of two pools inside the gland, one that is easily removed by exchange and osmotic shock, and the other which is not. The results obtained conform with the carrier model of Britten and McClure concerning the amino-acid pool in E. coli.