A smooth transition protocol for patients with multifocal motor neuropathy going from intravenous to subcutaneous immunoglobulin therapy: an open-label proof-of-concept study

Intravenous immunoglobulin (IVIG) is the first-line therapy for multifocal motor neuropathy (MMN). This open-label multi-centre study (NCT00701662) assessed the efficacy, safety, and convenience of subcutaneous immunoglobulin (SCIG) in patients with MMN over 6 months, as an alternative to IVIG. Eight MMN patients (42-66 years), on stable IVIG dosing, received weekly SCIG at doses equivalent to previous IVIG using a "smooth transition protocol". Primary efficacy endpoint was the change from baseline to week 24 in muscle strength. Disability, motor function, and health-related quality of life (HRQL) endpoints were also assessed. One patient deteriorated despite dose increase and was withdrawn. Muscle strength, disability, motor function, and health status were unchanged in all seven study completers who rated home treatment as extremely good. Four experienced 18 adverse events, of which only two were moderate. This study suggests that MMN patients with stable clinical course on regular IVIG can be switched to SCIG at the same monthly dose without deterioration and with a sustained overall improvement in HRQL.

A generalized anisotropic quadric yield criterion and its application to bone tissue at multiple length scales

Nonlinear computational analysis of materials showing elasto-plasticity or damage relies on knowledge of their yield behavior and strengths under complex stress states. In this work, a generalized anisotropic quadric yield criterion is proposed that is homogeneous of degree one and takes a convex quadric shape with a smooth transition from ellipsoidal to cylindrical or conical surfaces. If in the case of material identification, the shape of the yield function is not known a priori, a minimization using the quadric criterion will result in the optimal shape among the convex quadrics. The convexity limits of the criterion and the transition points between the different shapes are identified. Several special cases of the criterion for distinct material symmetries such as isotropy, cubic symmetry, fabric-based orthotropy and general orthotropy are presented and discussed. The generality of the formulation is demonstrated by showing its degeneration to several classical yield surfaces like the von Mises, Drucker–Prager, Tsai–Wu, Liu, generalized Hill and classical Hill criteria under appropriate conditions. Applicability of the formulation for micromechanical analyses was shown by transformation of a criterion for porous cohesive-frictional materials by Maghous et al. In order to demonstrate the advantages of the generalized formulation, bone is chosen as an example material, since it features yield envelopes with different shapes depending on the considered length scale. A fabric- and density-based quadric criterion for the description of homogenized material behavior of trabecular bone is identified from uniaxial, multiaxial and torsional experimental data. Also, a fabric- and density-based Tsai–Wu yield criterion for homogenized trabecular bone from in silico data is converted to an equivalent quadric criterion by introduction of a transformation of the interaction parameters. Finally, a quadric yield criterion for lamellar bone at the microscale is identified from a nanoindentation study reported in the literature, thus demonstrating the applicability of the generalized formulation to the description of the yield envelope of bone at multiple length scales.

The Determinants of Personal Income Tax Progressivity Around the Globe

This paper utilizes a novel database collected by the authors to document features of the progressivity of personal income tax systems across 209 countries for the years 1980-2009. We measure progressivity in several ways. First, we associate it with the increase in effective average (marginal) tax rates between a wage of zero and ten times the average wage in a country. Second, we consider the curvature of the tax schedule expressed as the difference between the effective average (marginal) tax schedule from a wage of zero to ten times the average wage and a linear average tax schedule and, alternatively, the diference between the effective average (marginal) tax schedule from the minimum positive taxable income, to ten times the average wage as opposed to a linear average tax schedule. Moreover, the paper assesses patterns regarding the conditional correlation of country-specifc tax progressivity measures with a host of economic and political country-specific characteristics and find the labor supply elasticity and the income replacement rates for the unemployed to be key determinants of progressivity around the globe, in line with economic theory.

Standing waves as an explanation for generic stationary correlation patterns in noninvasive EEG of focal onset seizures.

Cerebral electrical activity is highly nonstationary because the brain reacts to ever changing external stimuli and continuously monitors internal control circuits. However, a large amount of energy is spent to maintain remarkably stationary activity patterns and functional inter-relations between different brain regions. Here we examine linear EEG correlations in the peri-ictal transition of focal onset seizures, which are typically understood to be manifestations of dramatically changing inter-relations. Contrary to expectations we find stable correlation patterns with a high similarity across different patients and different frequency bands. This skeleton of spatial correlations may be interpreted as a signature of standing waves of electrical brain activity constituting a dynamical ground state. Such a state could promote the formation of spatiotemporal neuronal assemblies and may be important for the integration of information stemming from different local circuits of the functional brain network.

Effectiveness of fluorescence-based methods to detect in situ demineralization and remineralization on smooth surfaces.

This study aimed to evaluate the effectiveness of fluorescence-based methods (DIAGNOdent, LF; DIAGNOdent pen, LFpen, and VistaProof fluorescence camera, FC) in detecting demineralization and remineralization on smooth surfaces in situ. Ten volunteers wore acrylic palatal appliances, each containing 6 enamel blocks that were demineralized for 14 days by exposure to a 20% sucrose solution and 3 of them were remineralized for 7 days with fluoride dentifrice. Sixty enamel blocks were evaluated at baseline, after demineralization and 30 blocks after remineralization by two examiners using LF, LFpen and FC. They were submitted to surface microhardness (SMH) and cross-sectional microhardness analysis. The integrated loss of surface hardness (ΔKHN) was calculated. The intraclass correlation coefficient for interexaminer reproducibility ranged from 0.21 (FC) to 0.86 (LFpen). SMH, LF and LFpen values presented significant differences among the three phases. However, FC fluorescence values showed no significant differences between the demineralization and remineralization phases. Fluorescence values for baseline, demineralized and remineralized enamel were, respectively, 5.4 ± 1.0, 9.2 ± 2.2 and 7.0 ± 1.5 for LF; 10.5 ± 2.0, 15.0 ± 3.2 and 12.5 ± 2.9 for LFpen, and 1.0 ± 0.0, 1.0 ± 0.1 and 1.0 ± 0.1 for FC. SMH and ΔKHN showed significant differences between demineralization and remineralization phases. There was a negative and significant correlation between SMH and LF and LFpen in the remineralization phase. In conclusion, LF and LFpen devices were effective in detecting demineralization and remineralization on smooth surfaces provoked in situ.

Effectiveness of Fluorescence-based Methods in Monitoring Progression of Noncavitated Caries-like Lesions on Smooth Surfaces

Although there has been a significant decrease in caries prevalence in developed countries, the slower progression of dental caries requires methods capable of detecting and quantifying lesions at an early stage. The aim of this study was to evaluate the effectiveness of fluorescence-based methods (DIAGNOdent 2095 laser fluorescence device [LF], DIAGNOdent 2190 pen [LFpen], and VistaProof fluorescence camera [FC]) in monitoring the progression of noncavitated caries-like lesions on smooth surfaces. Caries-like lesions were developed in 60 blocks of bovine enamel using a bacterial model of Streptococcus mutans and Lactobacillus acidophilus . Enamel blocks were evaluated by two independent examiners at baseline (phase I), after the first cariogenic challenge (eight days) (phase II), and after the second cariogenic challenge (a further eight days) (phase III) by two independent examiners using the LF, LFpen, and FC. Blocks were submitted to surface microhardness (SMH) and cross-sectional microhardness analyses. The intraclass correlation coefficient for intra- and interexaminer reproducibility ranged from 0.49 (FC) to 0.94 (LF/LFpen). SMH values decreased and fluorescence values increased significantly among the three phases. Higher values for sensitivity, specificity, and area under the receiver operating characteristic curve were observed for FC (phase II) and LFpen (phase III). A significant correlation was found between fluorescence values and SMH in all phases and integrated loss of surface hardness (ΔKHN) in phase III. In conclusion, fluorescence-based methods were effective in monitoring noncavitated caries-like lesions on smooth surfaces, with moderate correlation with SMH, allowing differentiation between sound and demineralized enamel.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.