Virtual cavity in distributed Bragg reflectors.

We show theoretically and experimentally that distributed Bragg reflector (DBR) supports a surface electromagnetic wave exhibiting evanescent decay in the air and oscillatory decay in the DBR. The wave exists in TM polarization only. The field extension in the air may reach several wavelengths of light. Once gain medium is introduced into the DBR a novel class of diode lasers, semiconductor optical amplifiers, light-emitting diodes, etc. can be developed allowing a new type of in-plane or near-field light outcoupling. To improve the wavelength stability of the laser diode, a resonant cavity structure can be coupled to the DBR, allowing a coupled state of the cavity mode and the near-field mode. A GaAlAs-based epitaxial structure of a vertical-cavity surface-emitting laser (VCSEL) having an antiwaveguiding cavity and multiple GaInAs quantum wells as an active region was grown and processed as an in-plane Fabry-Pérot resonator with cleaved facets. Windows in the top stripe contact were made to facilitate monitoring of the optical modes. Three types of the optical modes were observed in electroluminescence (EL) studies under high current densities > 1 kA/cm2. Mode A with the longest wavelength is a VCSEL-like mode emitting normal to the surface. Mode B has a shorter wavelength, emitting light at two symmetric lobes tilted with respect to the normal to the surface in the direction parallel to the stripe. Mode C has the shortest wavelength and shifts with a temperature at a rate 0.06 nm/K. Polarization studies reveal predominantly TE emission for modes A and B and purely TM for mode C in agreement with the theory. Spectral position, thermal shift and polarization of mode C confirm it to be a coupled state of the cavity mode and near-field DBR surface-trapped mode.

Anti-waveguiding vertical-cavity surface-emitting laser at 850 nm: From concept to advances in high-speed data transmission.

Oxide-confined vertical cavity surface emitting lasers (VCSELs) with anti-waveguiding AlAs-rich core presently attract a lot of attention. Anti-waveguiding cavity enables the maximum possible optical confinement of the VCSEL mode ("λ/2 design"), increases its oscillator strength and reduces dramatically the optical power accumulated in the VCSEL mesa regions outside the aperture. VCSEL designs are suggested that favor single transverse mode operation. Modeling including current-induced and absorption-induced overheating shows that the preference for the transverse fundamental mode persists up to 10 mA current at 5 µm aperture diameter. Error-free data transmission is realized up to 160 Gb/s in digital-multitone (DMT) format using single-mode anti-waveguiding VCSELs. The approach to single-mode anti-waveguiding VCSELs is extended over a broad spectral range realizing error-free high-speed data transmission at both 850 nm and 910 nm.

[Reliability and Validity of the "Voice Handicap Index (VHI) Adapted to the Singing Voice"]. / Reliabilität und Validität des "Voice Handicap Index (VHI) adaptiert an die Gesangsstimme".

BACKGROUND: The Voice Handicap Index (i. e., VHI) is one of the most reliable standardized self-evaluation assessments in diagnosis of voice disorders. That tool is the most used in daily clinic. In 2007, the VHI was adapted to the singing population, called 'VHI adapté aux chanteurs'. The aim of our study was to investigate the reliability and validity of the German version of the VHI adapted to the singing voice. MATERIALS AND METHODS: 113 German singers (41 males and 72 females) with diverse singing styles and profession were included in the study. They were divided into 2 groups: a test-group (n=20) with self-perceived vocal complaints and a control-group (n=93) without vocal complaints. Statistical analysis to measure the reliability and validity was conducted with the Cronbach's alpha (i. e., Cron. α), independent t-test and receiver operating characteristics as well likelihood ratio, respectively. RESULTS: Reliability was confirmed by acceptable Cron. α (0.713-0.850) for each of the sub-scales and total score. The validity between the 2 groups showed high significant differences for each of the sub-scales and total score by which the test-group indicated higher scores than the control-group. Only the construct validity revealed no clear results. CONCLUSION: The VHI adapted to the singing voice is suited as reliable and valid standardized evaluation tool, but the diagnostic accuracy has to be investigated again because of too high inaccuracy in the interpretation of the outcome of the present data.

MiRNA let-7g regulates skeletal myoblast motility via Pinch-2.

Post-transcriptional regulation of gene expression by RNA-binding proteins and by small non-coding RNAs plays an important role in cell biology. Our previous results show that in murine skeletal myoblasts, the expression of Pinch-2, a focal adhesion remodeling factor that regulates cell motility, is repressed by an RNA-binding protein IMP-2/Igf2bp2. We now show that the expression of Pinch-2 is also regulated by the miRNA let-7g. Let-7g and IMP-2 repress Pinch-2 expression independently of each other. A knock-down of let-7g leads to an increase in Pinch-2 expression, and to a decrease of cell motility, which can be reversed by a simultaneous knock-down of Pinch-2. We conclude that let-7g controls the motility of mouse myoblasts in cell culture by post-transcriptionally regulating the expression of Pinch-2.

Invited review: Genetic contributions underlying the development of preimplantation bovine embryos.

In recent years, it has become evident that genetic selection to improve milk production has resulted in a decline in dairy cattle fertility. Growing evidence suggests that the greatest loss occurs early in pregnancy around the time of embryo implantation. As a means to make genetic improvements and to assist in reproductive performance, use of artificial reproductive technologies such as artificial insemination and in vitro production of embryos have been widely used. Both of these technologies rely on the competence and quality of gametes for successful development of embryos. Often, selection of animals is based on the genetic merit of the animal, although specific fertility markers are relatively underdeveloped compared with markers for production traits. Similarly, current in vitro fertilization systems could benefit from a uniform method for selection of the best quality embryos to transfer into recipients for successful implantation and delivery of healthy offspring. As genetics underlie biological processes such as fertility, the need exists to further identify and characterize genes that affect fertility and development within both the parental gametes and the embryo. Furthermore, the magnitude of the contribution of each parental genome to the success of embryo development and pregnancy is not clear. As such, the objective of this review is to provide an overview of studies relating to genetic markers at the DNA level, parental and embryonic gene expression, and the effects of epigenetics on embryonic development. Future studies should exploit advances in molecular technologies to identify and classify genes underlying fertility and development to establish biomarkers and predictors for improved genetic selection.

Genomic architecture of bovine κ-casein and ß-lactoglobulin.

The objective of this study was to characterize the genetic architecture underlying the absolute concentrations of 2 important milk proteins, κ-casein (κ-CN) and ß-lactoglobulin (ß-LG), in a backcross population of (Holstein × Jersey) × Holstein cattle. A genome-wide association analysis was performed using a selective DNA pooling strategy and the Illumina BovineHD BeadChip assay [777,000 (777K) SNP markers; Illumina Inc., San Diego, CA]. After correction for multiple testing, 25 single nucleotide polymorphisms were found to be associated with κ-CN and 36 single nucleotide polymorphisms were associated with ß-LG. A pathway association analysis revealed 15 Gene Ontology (GO) terms associated with the κ-CN trait and 28 GO terms associated with ß-LG. In addition, several GO terms were associated with both milk proteins. Further analysis revealed that κ-CN and ß-LG production is regulated by both kinase and phosphatase activity, including mechanisms regulating the extracellular matrix. These results are in concordance with the complex multihormonal process controlling the expression of milk proteins and interactions between mammary epithelial cells and extracellular matrix components. Although κ-CN and ß-LG milk proteins are expressed by single genes, the results from this study showed that many loci are involved in the regulation of the concentration of these 2 proteins.

Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin's lymphoma.

This prospective study assessed the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the staging and possible consequential changes of treatment regimen in patients with Hodgkin's lymphoma (HL). A total of 88 consecutive patients with histologically verified Hodgkin's lymphoma underwent a PET scan in addition to conventional staging procedures. Treatment was based on the conventional staging only, and the results of the FDG-PET did not affect the treatment strategy. The evaluation focused on the suggested change in clinical stage according to the Ann Arbor classification and on the suggested change in treatment strategy rather than on a lesion-by-lesion analysis. Using all the methods performed as the standard of reference, (18)F-FDG-PET staging was concordant with conventional staging in 70 out of 88 patients (80%). (18)F-fluorodeoxyglucose positron emission tomography suggested a change to a different clinical stage in 18 patients (20%). Management would have been changed in 16 patients (18%): intensification of treatment in nine patients (10%) and minimisation of treatment in seven patients (8%). In the 44 patients with early disease (stage IA-IIB), treatment would have been intensified in nine out of 44 patients (20%). (18)F-fluorodeoxyglucose positron emission tomography is a relevant noninvasive method that supplements conventional staging procedures and should therefore be used routinely to stage Hodgkin's lymphoma, particularly in patients with an early stage.

Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases.

Rhenium-188-HEDP ((188)Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of metastatic bone pain. As a product of (188)W/(188)Re generator, it is convenient for clinical therapeutic use with a short physical half-life of 16.9 h and a maximal beta-energy of 2.1 MeV. We investigated the effect of (188)Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 27 patients with bone metastases induced from prostate cancer. All patients were interviewed using a standardised set of questions before, and after therapy for 12 weeks. The patients were treated with 2700-3459 MBq of (188)Re-HEDP. Blood samples were taken weekly for 12 weeks, and a blood count was performed. Patients described an improvement on the Karnofsky performance scale from 74+/-7 to 85+/-9% 12 weeks after therapy (P=0.001). The pain score showed a maximum decrease from 44+/-18 to 27+/-20% in the third to the eight week after therapy (P=0.009). Seventy-six percent of the patients described a pain relief without increase of analgesic intake. Twenty percent of the patients could discontinue their analgesics and were pain free. Mean platelet count decreased from (286+/-75)*10(3) microl(-1) to (215+/-92)*10(3) microl(-1), and mean leucocyte count from (7.7+/-1.5)*10(3) microl(-1) to (6.0+/-1.9)*10(3) microl(-1) in the second to the fourth week after therapy. The maximal differences between the values of platelets and leucocytes before and after therapy were not statistically significant (P=0.021 and 0.094). In conclusion, (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain in prostate cancer and shows minimal bone marrow toxicity.

[Beta-radiation exposure at the finger tips during the radionuclide synovectomy]. / Beta-Ortsdosimetrie der Fingerkuppen bei der Radiosynoviorthese.

AIM: The radiation synovectomy is a widespread therapeutic option in rheumatoid arthritis. However, data for the beta-radiation exposure are rare. The aim of this study was to determine the personal dose equivalent H(P) (0.07) of the skin of the hands. METHODS: Thermo-luminescence detectors (TLDs) were attached at all fingertips of the therapist, the radiochemist and the nurse. In summary, the measurement of beta-exposure occurred in 155 joints at 6 days with different radio-nuclides ((169)Er, (186)Re, (90)Y). RESULTS: The greatest beta exposure were show at the forefinger (L-Ff) and thumb (L-Th) of the left hand, with which the therapist (right hander) fixed the injection needle. In 52 treated finger-joints (1204 MBq (169)Er), 29 treated large joints (2405 MBq (186)Re) and 15 treated knees (3100 MBq (90)Y) we found a cumulative beta exposure over all radionuclides of 190 mSv at L-Ff and 48 mSv at L-Th. The specific beta exposure for the individual radio-nuclides showed beta exposures of 0.56 mu Sv/MBq for (169)Er and 1.52 mu Sv/MBq for (186)Re-186 at the L-Ff. With using a manipulator the beta-exposure ((90)Y) could reduced from 22,09 to 0.42 mu Sv/MBq at the L-Ff. The greatest beta exposures for the radiochemist was 119 mSv at the L-Ff for all radionuclides. CONCLUSION: In usual techniques of radiation synovectomy the (90)Y produced the greatest part of radiation exposure. Especially at the L-Ff it might exceed the German limit for the official dosimetry service at the skin ( section sign 55 Strl-SchV). Using a holding forceps we can keep the legal rules and can reduce considerably the beta exposure.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

[Late complications after transcatheter closure of atrial septal defect]. / Spätkomplikation nach katheterinterventionellem Vorhofseptumdefektverschluss.

The transcatheter closure of atrial septal defects is generally accepted as an alternative to surgical therapy in selected patients. Potential complications of these devices are a matter of concern, as well as the very complicated implantation technique required for some systems. We report on a 17 year old patient in whom embolization of a fractured umbrella arm into a peripheral branch of the left pulmonary artery occurred. A 35 mm-ASDOS-Device (protected trademark of the Dr. Osypka GmbH/Grenzach-Wyhlen, Germany) had been implanted 4 years ago. The perfusion scintigraphy of the left lung showed normal pulmonary blood flow. Echocardiography failed to demonstrate instability of the double-umbrella device. The patient was always free of any symptoms. Due to the permanent stresses between device and heart, late fractures of the device and embolizations of fragments are possible. It can be concluded that patients who underwent transcatheter closure of an ASD require lifelong follow-up.

Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.

AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept of alpha1-protease inhibitor deficiency?

UNLABELLED: The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.

Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma.

The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.

Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow.

It is well established that myocardial blood flow is heterogeneous on the local level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studies have been performed: enzyme activity and tissue metabolite level assessments. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated Vmax values, local substrate affinity (Km values) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable insight has been obtained concerning flow-metabolism matching from tissue metabolite measurements, especially when connected with mathematical model analyses. The latter permitted the calculation of metabolic flux rates (e.g., production of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologically meaningful local metabolite concentrations (e.g., free cytosolic adenosine). The bottom line of the studies reported to date is that the broad range of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenergic stimulation. Thus, high flow samples exhibit a higher oxidative metabolism than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The importance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the myocardium under control conditions, i.e., the local level of flow-metabolism matching.

Assessment of management options in marine fisheries by qualitative modelling techniques.

An effective management of the rapidly dwindling marine fish resources is of great ecological, economic and social importance for the future. An over-development of commercial fisheries has brought about a multitude of negative environmental impacts, such as an accelerated exploitation of stocks or a decrease of marine biodiversity, and furthermore, a profound structural change in fish industry. However, the main reason for the non-prosperous rationing of marine resources is the lack of knowledge about certain processes as well as the non-availability of adequate steering instruments. This paper addresses the lack of conceptualization in the case of uncertain knowledge. It proposes a model approach which can be used for weak but improved decision support under the premise of vague knowledge. The usage of qualitative differential equations illustrates general patterns of overcapitalization of fishing fleets. The extension of traditional model approaches by integration of additional socio-economic phenomena in this context supplies deeper insights in the dynamics of a coupled economic and ecological system. The approach provides a set of characteristic system behaviours which can be fruitfully used for the development of future management tasks.