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Colette Mankowski,1 Divine Ikenwilo,2,† Sebastian Heidenreich,2 Mandy Ryan,2 Jameel Nazir,1 Cathy Newman,1 Verity Watson2 1Health Economics and Outcomes Research, Astellas Pharma Europe Ltd., Chertsey, 2Health Economics Research Unit, University of Aberdeen, Aberdeen, UK †Dr Ikenwilo passed away on November 27, 2015 Objective: To explore and quantify men’s preferences and willingness to pay (WTP) for attributes of medications for lower urinary tract symptoms associated with benign prostatic hyperplasia using a discrete choice experiment. Subjects and methods: Men in the UK aged ≥45 years with moderate-to-severe lower urinary tract symptoms/benign prostatic hyperplasia (based on self-reported International Prostate Symptom Score ≥8) were recruited. An online discrete choice experiment survey was administered. Eligible men were asked to consider different medication scenarios and select their preferred medication according to seven attributes: daytime and nighttime (nocturia) urinary frequency, urinary urgency, sexual and nonsexual side effects, number of tablets/day, and cost/month. A mixed-logit model was used to estimate preferences and WTP for medication attributes. Results: In all, 247 men completed the survey. Men were willing to trade-off symptom improvements and treatment side effects. Men preferred medications that reduced urinary urgency and reduced day- and nighttime urinary frequency. Men preferred medications without side effects (base-case level), but did not care about the number of tablets per day. WTP for symptomatic improvement was £25.33/month for reduced urgency (urge incontinence to mild urgency), and £6.65/month and £1.39/month for each unit reduction in night- and ­daytime urination frequency, respectively. The sexual and nonsexual side effects reduced WTP by up to £30.07/month. There was significant heterogeneity in preferences for most attributes, except for reduced urinary urgency from urge incontinence to mild urgency and no fluid during ejaculation (dry orgasm). Conclusion: To compensate for side effects, a medicine for lower urinary tract symptoms/benign prostatic hyperplasia must provide a combination of benefits, such as reduced urgency of urination plus reduced nighttime and/or reduced daytime urination. Keywords: benign prostatic hyperplasia, discrete choice experiment, erectile dysfunction, lower urinary tract symptoms, storage symptoms, urge incontinence

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the present paper, we propose a 2D-Fourier transform method as a simple and efficient algorithm for stochastical and numerical studies to investigate the systematic impacts of line edge roughness on light diffraction pattern of periodic line-space structures. The key concept is the generation of ensembles of rough apertures composed of many slits, to calculate the irradiance of the illuminated rough apertures far away from the aperture plane, and a comparison of their light intensities to those of the undisturbed, ’non-rough’ aperture. We apply the Fraunhofer approximation and interpret the rough apertures as binary 2D-gratings to compute their diffraction patterns very efficiently as the 2D-Fourier transform of the light distribution of the source plane. The rough edges of the aperture slits are generated by means of power spectrum density (PSD) functions, which are often used in metrology of rough geometries. The mean efficiencies of the rough apertures reveal a systematic exponential decrease for higher diffraction orders if compared to the diffraction pattern of the unperturbed aperture. This confirms former results, obtained by rigorous calculations with computational expensive finite element methods (FEM) for a simplified roughness model. The implicated model extension for scatterometry by an exponential damping factor for the calculated efficiencies allows to determine the standard deviation σr of line edge roughness along with the critical dimensions (CDs), i.e., line widths, heights and other profile properties in the sub-micrometer range. First comparisons with the corresponding roughness value determined by 3D atomic force microscopy (3D AFM) reveal encouraging results.

The refractive index of a y‐cut SiO2 crystal surface is reconstructed from orientation‐dependent soft X‐ray reflectometry measurements in the energy range from 45 to 620 eV. Owing to the anisotropy of the crystal structure in the (100) and (001) directions, a significant deviation of the measured reflectance at the Si L2,3 and O K absorption edges is observed. The anisotropy in the optical constants reconstructed from these data is also confirmed by ab initio Bethe–Salpeter equation calculations for the O K edge. This new experimental data set expands the existing literature data for quartz crystal optical constants significantly, particularly in the near‐edge regions. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The impact of line edge roughness (LER) on measured light diffraction pattern of photo masks is investigated. This is relevant for scatterometry as an accurate, indirect method in wafer metrology to determine geometry parameters of periodic surface structures from scattered light intensities. The sensitivity to roughness increases the smaller the wavelength of the incident light is. For EUV scatterometry at 13.5 nm, the efficiencies of many higher diffraction orders can be measured. In the nanometer range they are sensitive to deviations from the ideal periodic straight line structure such as LER. Applying the Fraunhofer approximation, we calculate the far field diffraction pattern of an illuminated 2D aperture plane composed of many rough slits by its 2D-Fourier transform. The rough edges of the aperture gaps are created by means of power spectrum density (PSD) functions used with a random complex exponential phase term. A simple theory neglecting correlation in the roughness profile predicts for the intensities an exponential decrease with the diffraction order and the standard deviation of the roughness amplitude which can be tested by our numerical solutions. The calculated light intensities for a rough aperture are compared with the ones found for an ideal periodic aperture whose edges are straight lines. Ensembles of rough apertures with different values for the imposed standard deviation of the roughness amplitude σ , the linear correlation length ξ , and the roughness exponent α were examined. The validity of the exponential decrease was investigated for correlation lengths ξ from 5 nm up to 1000 nm and roughness exponents α from 0.3 to 1.0. It was found that the results for the exponential correction factor deviate substantially from the mentioned theoretical value for large correlation lengths and small roughness exponents. [ABSTRACT FROM AUTHOR]

With the global shift towards more person-centred approaches to care, where patients and clinicians engage in a shared decision-making partnership to identify the treatment best suited to an individual, it is important to understand all aspects of care that patients value in specific contexts and indications. The three main themes were (1) burden of symptoms (2) diagnosis of endometriosis, and (3) treatment of endometriosis. The identified themes were used to develop a DCE to measure preference heterogeneity in treatment preferences for recurrence endometriosis. [Extracted from the article]

Objective: In renal transplantation most initial immunosuppressive regimen comprise triple therapy which is maintained over months or years inspite of numerous side effects. Methods: We treated 8 patients with tacrolimus monotherapy after 3 months (n = 4) and because of excellent results already after 7 days (n = 4). Monotherapy was preceeded by a tacrolimus/prednisolone combination with or without MMF or sirolimus. Patients with first renal transplants and normal immunological risk after cadaveric (n = 6), nonheart beating (n = 1) or living (n = 1) donation were included. Results: After a mean follow-up of 5 years, 7 patients had an excellent renal function (s.-creatinine 1.2 ± 0.4 mg/dl) without occurrence of any rejection and only one case of ATN. One patient had lost his transplant (non-heart beating donor) because of chronic allograft nephropathy and non-compliance after 76 months. Hypertension appeared only in 4 patients with good compensation by monotherapy in 3 patients. Post-transplant diabetes occurred in 3 patients and persisted in two. Hypercholesterolemia was present and treated by statins only in two patients. SDS-PAGE electrophoresis of urinary samples revealed an excellent protection of glomerular and tubular integrity. Of special note, mean trough levels of tacrolimus of 8.5 ± 1.5 ng/ml were achieved by daily intake of only 4.2 ± 1.1 mg/day. Conclusions: In summary, very early tacrolimus monotherapy after renal transplantation is safe to prevent rejections and offers important advantages with respect to low occurrence of hypertension and hyperlipidemia. Interestingly, glucocorticoids seem to interact with cytochrom P450 3A4 so that after steroid withdrawal small doses of tacrolimus lead to good trough blood levels. [ABSTRACT FROM AUTHOR]

Objective: The incidence of acute rejection in renal transplantation has been dramatically reduced by the introduction of highly effective immunosuppressive drugs as cyclosporin A and rapamycin. Nevertheless chronic rejection is a main problem in transplantation. Immunological processes but also accelerated vascular disease contribute to this problem. This may be due to ongoing activation of proinflammatory cells. Especially monocytes/macrophages induce via disturbed stress responses vascular tissue remodeling and atherosclerosis. TF is the major initiator of the blood coagulation process. Besides thrombogenesis, TF is involved in angiogenesis and metastasis development and has direct pro-inflammatory effects by inducing the production of reactive oxygen species. Therefore we investigated the regulation of the expression of TF in human monocytes, cells which infiltrate the allograft and are able to promote long-lasting deleterious effects. Methods: Freshly isolated human monocytes were stimulated by rapamycin and LPS. At mRNA level TF was measured by semiquantitative RT-PCR. Protein expression of TF factor was detected by FACS analysis. TF activitiy was measured by a chromogenic assay. Rapamycin induced TF in a dose dependent fashion. Results: 500 ng/ml rapamycin induced the same activity of TF as the positive control LPS. Additionally stimulation with IL-4 as a TH2 cytokine with antiinflammatory effects prevented the expression of TF acitivity induced by rapamycin or LPS. Blocking protein kinase C by calphostin led to an abrogation of TF induction by rapamycin. Conclusions: In conclusion, we could show that rapamycin, in contrast to cyclosporin A, induced TF in human monocytes which may be associated with enhanced thrombogenesis observed in immunosuppressed patients. Further studies will show whether this effect is also linked to the anti-tumor effect of rapamycin. [ABSTRACT FROM AUTHOR]