Highly nonlinear yttrium-aluminosilicate optical fiber with a high intrinsic stimulated Brillouin scattering threshold.

Highly nonlinear (high-NA small-mode-area) optical fibers also possessing an intrinsically high stimulated Brillouin scattering threshold are described. More specifically, silica clad, yttrium-aluminosilicate core fibers are shown to exhibit an intrinsically low Brillouin gain coefficient between 0.125 and 0.139×10-11 m/W and a Brillouin gain linewidth of up to 500 MHz. Losses on the order of 0.7 dB/m were measured, resulting from impurities in the precursor materials. Nonlinear refractive index values are determined to be similar to that of silica, but significant measurement uncertainty is attributed to the need to estimate dispersion curves since their direct measurement could not be made. The interest for highly nonlinear optical fibers with a low intrinsic Brillouin gain coefficient is expected to continue, especially with the growing developments of narrow-linewidth high-energy laser systems.

[A surgical micromanipulator in ear surgery: potential and comparison to freehand preparation]. / Ein chirurgischer Mikromanipulator in der Ohrchirurgie: Potenzial und Vergleich mit der freien Präparation.

INTRODUCTION: Surgical accuracy in microscopic ear surgery is reduced by limited access and tremor. At this point a micromanipulator could have a positive influence. The goal of the study was: 1. To develop a system that would enable measurements of accuracy, time and precision during a manual approach to the middle ear 2. To apply a manipulator that can easily be a compact part of the regular setup in ear surgery 3. To compare the manual results critically considering accuracy and tremor reduction and to compare these results with those of a manipulator A manipulator in ear surgery does not need to be a highly complex structure with force feedback and multiple degrees of freedom. The surgeon's preparation in middle ear surgery is most of the time straight without potentially applying the 15 degrees of freedom the human hand can offer. The micromanipulator in this study was developed in order to serve as a compact, teleoperated instrument without limiting the surgeon's dexterity. The use of standard instruments facilitates the integration of the system in existing surgical procedures and sterilisation concepts. MATERIAL AND METHODS: Ten head and neck surgeons simulated an approach to the stapedial footplate on a modified 3D cast of a realistic human skull in an experimental OR. A perforator was moved to a reference point on the stapedial footplate. The movements were detected by means of an image acquisition system. Each trial was repeated more than 200 times, aiming both manually and with the aid of a micromanipulator (> 4,000 measurements). RESULTS: Accuracy for the manual and micromanipulator approach revealed no considerable differences. In absolute terms, the manual approach was more accurate. However, the learning curves indicated a stronger decrease in deviation when the micromanipulator was used and also less deviation in scatter plots. At the beginning, the time required for pointing increased when using the micromanipulator, but decreased to a greater extent in the course of the trial when compared to the manual approach. The work strain was distinctively lower when the micromanipulator was applied. CONCLUSION: The micromanipulator gave evidence of a stronger effect as regards individual improvement in accuracy and time span. The micromanipulator shows potential for improvements in accuracy as well as compensation for poor ergonomics.

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

Manual accuracy in comparison with a miniature master slave device--preclinical evaluation for ear surgery.

Manual accuracy in microsurgery is reduced by tremor and limited access. A surgical approach through the middle ear also puts delicate structures at risk, while the surgeon is often working at an unergonomic position. At this point a micromanipulator could have a positive influence. A system was developed to measure "working accuracy", time and precision during manipulation in the middle ear. 10 ENT-surgeons simulated a perforation of the stapedial footplate on a modified 3D print of a human skull in a mock OR. Each trial was repeated more than 200 times aiming manually and using a micro-manipulator. Data of over 4000 measurements was tested and graphically processed. Work strain was evaluated with a questionnaire. Accuracy for manual and micromanipulator perforation revealed a small difference. Learning curves showed a stronger decrease both in deviation and time when the micromanipulator was used. Also a lower work strain was apparent. The micromanipulator has the potential as an aiding device in ear surgery.

Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex.

Rab GTPases are central elements of the vesicular transport machinery. An emerging view is that downstream effectors of these GTPases are multiprotein complexes that include nucleotide exchange factors to ensure coupling between GTPase activation and effector function. We have previously shown that Rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of Rabex-5, a Rab5 nucleotide exchange factor, and the effector Rabaptin-5. We postulated that the physical association of these two proteins is necessary for their activity in Rab5-dependent endocytic membrane transport. To evaluate the functional implications of such complex formation, we have reconstituted it with the use of recombinant proteins and characterized its properties. First, we show that Rabaptin-5 increases the exchange activity of Rabex-5 on Rab5. Second, Rab5-dependent recruitment of Rabaptin-5 to early endosomes is completely dependent on its physical association with Rabex-5. Third, complex formation between Rabaptin-5 and Rabex-5 is essential for early endosome homotypic fusion. These results reveal a functional synergy between Rabaptin-5 and Rabex-5 in the complex and have implications for the function of analogous complexes for Rab and Rho GTPases.

Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A1.

HLA-G is a class I gene that is expressed in the extravillous cytotrophoblast. Although the function of this gene is still unknown, its expression at the maternal-fetal interface suggests that HLA-G may play a key role in the induction of tolerance during pregnancy. Preliminary to our studies of the effects of HLA-G polymorphisms on pregnancy outcome, we have defined HLA-G alleles in the Hutterites. We report here the presence of nine HLA-G alleles that differ with respect to nucleotide sequences, including four groups of alleles that differ with respect to amino acid sequences, and striking linkage disequilibrium between HLA-G and HLA-A alleles. The levels and sites of polymorphism in HLA-G suggest that this gene had a unique evolutionary history and may perform nonclassical functions at the maternal-fetal interface.

Simultaneous lupus anticoagulant and anticardiolipin assays and clinical detection of antiphospholipids.

Lupus anticoagulants and/or anticardiolipin antibodies were detected in 100 patients with autoimmune disorders, thrombosis, or pregnancy loss. Significant agreement between tests for these two antiphospholipid activities was lacking. Performing both assays is thus important in maximizing the likelihood of detecting antiphospholipids that may have clinical relevance.

Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations.

We utilized a kaolin-activated partial thromboplastin time (APTT) using rabbit brain phospholipid, in which the capacity of a fourfold increased "high" phospholipid concentration (PC) to normalize the abnormal "standard" PC-APTT in patients with lupus anticoagulants is assessed. This system was also used to measure factors VIIIC, IX, and XI. The tissue thromboplastin inhibition test (TTI), a prothrombin time system in which the activity of a lupus anticoagulant is unmasked by the use of dilute thromboplastin, was simultaneously evaluated. Test sensitivity was defined by results on 31 consecutive patients with standard PC-APTT inhibitors and no bleeding tendency. Specificity was based on 94 patients with various other coagulopathies, including coagulation factor inhibitors, severe congenital factor deficiencies, hepatic insufficiency, and warfarin and heparin treatment. Twenty-one patients with lupus erythematosus and standard PC-APTT results within normal limits were also tested. Sensitivity of the APTT system was superior to that of the TTI (97% v 58%); high PC normalized clotting time ratios and factor levels. Positive results were common with both assays in the group of 20 heparinized patients. The APTT system had superior specificity in remaining cases; there were no positive tests among 74 patients. The lupus erythematosus group had a significant decrease in the clotting time ratio with high PC, indicating that low-level lupus anticoagulants are quite prevalent in this group. The kaolin clotting time using rabbit brain phospholipid in standard and high concentrations is a simple, sensitive, and specific technique for diagnosis of lupus anticoagulants.

Nitric oxide and prostacyclin inhibit fetal platelet aggregation: a response similar to that observed in adults.

OBJECTIVE: We evaluated the relative importance of two endothelium-derived substances, prostacyclin and nitric oxide, in their ability to inhibit aggregation of fetal and maternal platelets. STUDY DESIGN: The effects of various concentrations of prostacyclin and S-nitroso-N-acetylpenicillamine (which releases nitric oxide) on platelet aggregation were studied by means of platelet-rich plasma from at least five to six subjects per group. Fetal blood was collected from umbilical vein at delivery. Maternal venous blood was collected within 4 hours of delivery. Platelet aggregation was monitored with a platelet aggregation profiler. Adenosine diphosphate was used as the aggregating agent. Statistical differences between means were evaluated with two-way analysis of variance or Student t test. RESULTS: Prostacyclin and S-nitroso-N-acetylpenicillamine inhibited aggregation of fetal and maternal platelets, but prostacyclin was more potent. Fetal platelets were more sensitive than maternal platelets to prostacyclin and S-nitroso-N-acetylpenicillamine. CONCLUSION: Prostacyclin appears to be more important in preventing aggregation of platelets in the feto placental circulation.