The impact of firm and industry characteristics on small firms’ capital structure

We investigate small firms’ capital structure, employing a proprietary database containing financial statements of Dutch small and medium-sized enterprises (SMEs) from 2003 to 2005. We find that the capital structure decision of Dutch SMEs is consistent with the pecking order theory: SMEs use profits to reduce their debt level, and growing firms increase their debt position since they need more funds. Furthermore, we document that profits reduce in particular short term debt, whereas growth increases long term debt. This implies that when internal funds are depleted, long term debt is next in the pecking order. We also find evidence for the maturity matching principle in SME capital structure: long term assets are financed with long term debt, while short term assets are financed with short tem debt. This implies that the maturity structure of debt is an instrument for lenders to deal with problems of asymmetric information. Finally, we find that SME capital structure varies across industries but firm characteristics are more important than industry characteristics.

Educational Utopia? the New Zealand Standards Approach Considered in the Light of the German Experience in Vocational Training

This thesis is concerned with both the direction and the appropriateness of the recently adopted standards-based approach in post-compulsory education and training in New Zealand, while particularly focusing on the implications this might have in formal post-school trades training. It evaluates the developments, the tenets, and the early results of the 'standards' movement within a socio-historical context and against the development of relevant policy formations and legislative changes. The central focus in this work is on the National Qualifications Framework, which is currently being developed under the auspices of the New Zealand Qualifications Authority. This outcomes-focussed model, and related government-initiatives, represent a radial shift away from established learning and teaching practices in New Zealand, a move which is not uncontested for both pedagogical and pragmatical reasons. An analysis of these developments is discussed with reference to those in apprenticeship training and policy in the Federal Republic of Germany, which includes the intention, as expressed by the major role players in the Republic, to develop an educational framework model. The principles, scope, and structure, as they relate to these framework models, are analysed from a comparative perspective, and certain points are highlighted. This thesis contends that despite fundamental divergence in training cultures and systems in the two countries, it is recognised that the common aim of the framework approaches is to improve the correspondence between the world of education and work as well as to enhance the educational pathways for students. This, it is argued, are commendable and valuable aims; not in the least because it has also the potential to bridge the 'vocational/academic' divide - an increasingly invalid division in modern-day societies. This is reflected in a strong focus in these framework models on the promotion, and implementation, of an integrated learning and teaching approach which is supported by the notion introduced by Michael Young that qualifying is a continuous process. This concept is now generally endorsed by the major role players in both Germany and New Zealand as being an important one, in that it is supportive of the macro aim of furthering national economic progress. The author, however, contends that educational, progress cannot simply be assumed because a new educational, or qualifications, framework is being introduced. Its foundation needs to be pedagogically sound and based on sufficient research while an (over)reliance on a single assessment strategy for application to all of post-compulsory education and training cannot be accepted as valid from an educational viewpoint. The thesis concludes with advocacy for more critical research into the NQF

Clinical Implications of Non-Steatotic Hepatic Fat Fractions on Quantitative Diffusion-Weighted Imaging of the Liver

Diffusion-weighted imaging (DWI) is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF) are higher than 5.5% (steatosis). However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0) were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T-2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM) model. Four circular regions (circle divide 22.3 mm) were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF 5.5%). DWI parameters and T-2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49610 23 mm(2)/s) and T-2* (32.2, 27.2 and 21.0 ms) differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%). Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = -0.514,

T1 vs. T2 weighted magnetic resonance imaging to assess total kidney volume in patients with autosomal dominant polycystic kidney disease

Purpose: In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences. Methods: 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses. Results: Participants were 49.7 +/- 7.0 years of age, 55.0% female, with estimated GFR of 50.1 +/- 11.5 mL/min/1.73 m(2). CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 +/- 0.3 years was similar for T2 and T1 (9.3 +/- 10.6% vs. 7.8 +/- 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P <0.001). Conclusions: In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability

Estimation of Nuwiq® (simoctocog alfa) activity using one-stage and chromogenic assays-Results from an international comparative field study.

BACKGROUND Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy. FVIII C can be measured by one-stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability. AIMS This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq® (human-cl rhFVIII, simoctocog alfa), a fourth-generation recombinant human FVIII produced in a human cell line. METHODS FVIII-deficient plasma was spiked with Nuwiq® or Advate® at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter- and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed. RESULTS Forty-nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq® :Advate® ) of 1.02-1.13. Mean recoveries ranged from 97% to 191% for Nuwiq® , and from 93% to 172% for Advate® , with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq® and from 1.01 to 1.17 for Advate® . CONCLUSIONS Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq® in routine laboratory practice, without the need for a product-specific reference standard

Effects of microperfusion in hepatic diffusion weighted imaging

Clinical hepatic diffusion weighted imaging (DWI) generally relies on mono-exponential diffusion. The aim was to demonstrate that mono-exponential diffusion in the liver is contaminated by microperfusion and that the bi-exponential model is required. Nineteen fasting healthy volunteers were examined with DWI (seven b-values) using fat suppression and respiratory triggering (1.5 T). Five different regions in the liver were analysed regarding the mono-exponentially fitted apparent diffusion coefficient (ADC), and the bi-exponential model: molecular diffusion (D (slow) ) microperfusion (D (fast) ) and the respective fractions (f (slow/fast)). Data were compared using ANOVA and Kruskal-Wallis tests. Simulations were performed by repeating our data analyses, using just the DWI series acquired with b-values approximating those of previous studies. Median mono-exponentially fitted ADCs varied significantly (P <0.001) between 1.107 and 1.423 x 10(-3) mm(2)/s for the five regions. Bi-exponential fitted D-slow varied between 0.923 and 1.062 x 10(-3) mm(2)/s without significant differences (P = 0.140). D (fast) varied significantly, between 17.8 and 46.8 x 10(-3) mm(2)/s (P <0.001). F-tests showed that the diffusion data fitted the bi-exponential model significantly better than the mono-exponential model (F > 21.4, P <0.010). These results were confirmed by the simulations. ADCs of normal liver tissue are significantly dependent on the measurement location because of substantial microperfusion contamination; therefore the bi-exponential model should be used. Diffusion weighted MR imaging helps clinicians to differentiate tumours by diffusion properties Fast moving water molecules experience microperfusion, slow molecules diffusion Hepatic diffusion should be measured by bi-exponential models to avoid microperfusion contamination Mono-exponential models are contaminated with microperfusion, resulting in apparent regional diffusion differences Bi-exponential models are necessary to measure diffusion and microperfusion in the liver

Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients

Feasibility studies for the measurement of time-like proton electromagnetic form factors from p¯ p→ μ+μ- at P ¯ ANDA at FAIR

This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, | GE| and | GM| , using the p¯ p→ μ+μ- reaction at P ¯ ANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at P ¯ ANDA , using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is p¯ p→ π+π-, due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented

Educational Utopia? the New Zealand Standards Approach Considered in the Light of the German Experience in Vocational Training

This thesis is concerned with both the direction and the appropriateness of the recently adopted standards-based approach in post-compulsory education and training in New Zealand, while particularly focusing on the implications this might have in formal post-school trades training. It evaluates the developments, the tenets, and the early results of the 'standards' movement within a socio-historical context and against the development of relevant policy formations and legislative changes. The central focus in this work is on the National Qualifications Framework, which is currently being developed under the auspices of the New Zealand Qualifications Authority. This outcomes-focussed model, and related government-initiatives, represent a radial shift away from established learning and teaching practices in New Zealand, a move which is not uncontested for both pedagogical and pragmatical reasons. An analysis of these developments is discussed with reference to those in apprenticeship training and policy in the Federal Republic of Germany, which includes the intention, as expressed by the major role players in the Republic, to develop an educational framework model. The principles, scope, and structure, as they relate to these framework models, are analysed from a comparative perspective, and certain points are highlighted. This thesis contends that despite fundamental divergence in training cultures and systems in the two countries, it is recognised that the common aim of the framework approaches is to improve the correspondence between the world of education and work as well as to enhance the educational pathways for students. This, it is argued, are commendable and valuable aims; not in the least because it has also the potential to bridge the 'vocational/academic' divide - an increasingly invalid division in modern-day societies. This is reflected in a strong focus in these framework models on the promotion, and implementation, of an integrated learning and teaching approach which is supported by the notion introduced by Michael Young that qualifying is a continuous process. This concept is now generally endorsed by the major role players in both Germany and New Zealand as being an important one, in that it is supportive of the macro aim of furthering national economic progress. The author, however, contends that educational, progress cannot simply be assumed because a new educational, or qualifications, framework is being introduced. Its foundation needs to be pedagogically sound and based on sufficient research while an (over)reliance on a single assessment strategy for application to all of post-compulsory education and training cannot be accepted as valid from an educational viewpoint. The thesis concludes with advocacy for more critical research into the NQF

Assessment of the link between quantitative biexponential diffusion-weighted imaging and contrast-enhanced MRI in the liver

Purpose: To investigate if intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) can be linked to contrast-enhanced (CE-)MRI in liver parenchyma and liver lesions. Methods: Twenty-five patients underwent IVIM-DWI followed by multiphase CE-MRI using Gd-EOB-DTPA (n = 20) or Gd-DOTA (n = 5) concluded with IVIM-DWI. Diffusion (D-slow), microperfusion (D-fast), its fraction (f(fast)), wash-in-rate (R-early) and late-enhancement-rate (R-late) of Gd-EOB-DTPA were calculated voxel-wise for the liver. Parenchyma and lesions were segmented. Pre-contrast IVIM was compared 1) between low, medium and high R-early for parenchyma 2) to post-contrast IVIM substantiated with simulations 3) between low and high R-late per lesion type. Results: D-fast and f(fast) increased (P <0.001) with 25.6% and 33.8% between low and high R-early of Gd-EOB-DTPA. New decreased (-15.0%; P <0.001) with increasing R-early. Gd-DOTA demonstrated similar observations. f(fast) (+10%; P <0.001) and D-fast (+6.6%; P <0.001) increased after Gd-EOB-DTPA, while decreasing after Gd-DOTA (-4.2% and 5.7%, P <0.001) and were confirmed by simulations. For focal nodular hyperplasia lesions (n = 5) D-fast and f(fast) increased (P <0.001) with increasing R-late, whereas for hepatocellular carcinoma (n = 4) and adenoma (n = 7) no differences were found. Conclusion: Microperfusion measured by IVIM reflects perfusion in a way resembling CE-MRI. Also IVIM separated intra- and extracellular MR contrast media. This underlines the potential of IVIM in quantitative liver imaging. (C) 2016 Elsevier Inc. All rights reserved