Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.     

Purification and properties of beta-N-Acetylhexosaminidase from cabbage

beta-N-Acetylhexosaminidase was purified from the extract of cabbage by sequential steps of ammonium sulfate fractionation, chromatofocusing, DEAE-Sepharose CL-6B ion exchange chromatography and Sephacryl S-200 HR gel filtration. By these steps, the purity of the enzyme increased by 256 fold with a recovery of 8%. The purified enzyme was homogeneous as examined by native PAGE. It showed an optimal pH of 4, an optimal temperature of 60 degrees C and a Km of 0.94 mM for hydrolysis of pNp-beta-GlcNAc. The molecular mass of the enzyme determined from filtration through Sephacryl S-200 was 150 kDa. Three subunits with molecular mass of 64, 57 and 51 kDa were observed as determined by SDS-PAGE. NBS (0.025 mM), DEPC (3 mM) and WRK (30 mM) significantly inhibited the activity of the enzyme. The enzyme also showed activity toward pNp-beta-GalNAc, N,N'-diacetylchitobiose, N,N',N"-triacetylchitotriose and N,N',N",N"'-tetraacetyl chitotetraose but showed no activity toward pNp-alpha-GlcNAc, chitin and ethylene glycol chitin.     

Radiotherapy of plantar heel spurs: indications, technique, clinical results at different dose concepts

BACKGROUND: In a retrospective study the efficacy of orthovoltage radiotherapy for refractory painful plantar heel spur was analyzed for 3 different radiation dose concepts. PATIENTS AND METHODS: From 1.1 1984 through 1.3.1994, 182 patients with refractory painful heel symptoms and radiologically proven plantar heel spur received radiotherapy. A total of 141 patients and 170 heels (due to double-sided symptoms) were completely documented in long-term follow-up. Clearly defined semi-quantitative criteria (9-point score) were used to analyze heel pain and ankle function prior to RT, 6 to 12 weeks post-radiation, and at last follow-up. The treatment outcome, i.e. (un)favourable response, of 3 radiation dose concepts were compared: Group A (n = 72 heels) received 12 Gy total radiation dose in 3 fractions per week and 2 series (6 x 1 Gy per series) separated by 6 weeks; group B (n = 98 heels) received 3 Gy total radiation dose in 10 fractions of 0.3 Gy (n = 50) or 5 Gy (10 x 0.5 Gy) (n = 48) with conventional fractionation in 1 series. RESULTS: Radiotherapy was very effective: at last follow-up 67% (group A) and 71% (group B) remained completely free of pain. The rate of "complete pain relief" (i.e. free of any pain symptoms) was not different between the 3 radiation concepts. However, significant differences were observed with regard to "incomplete or insufficient pain relief", i.e. a subjective pain relief of less than 80%, a delayed pain relief after more than 4 weeks or a relapse of pain symptoms in long-term follow-up. More favourable results were achieved in patients receiving 5 Gy or 12 Gy total dose, while patients with 3 Gy total dose had significantly worse results. Prognostic factors for "complete pain relief" were short duration of pain symptoms and acute pain symptoms prior to radiotherapy; with regard to "in-complete or insufficient pain relief" the total dose was found to be a prognostic parameter. CONCLUSIONS: Patients with refractory heel pain can yield a high response to radiotherapy even after failing various conventional treatments previously. Thus, radiotherapy should not be solely regarded as a last resort due to its low costs and high efficacy at low radiation doses.     

Progressive subretinal fibrosis and blindness in patients with multifocal granulomatous chorioretinitis

Since women with a first-degree relative with breast cancer are at increased risk for breast cancer, it is of special importance that they adhere to early detection programs. In this study, women with (389) and without (3295) a family history of breast cancer were compared with respect to risk perception, breast cancer anxiety, and early detection behavior. Special attention was paid to the role of knowing that family history is a breast cancer risk factor. It was found that 46% of "family history positives" did not know that their risk was increased by their family history. Still, family history positives had increased risk perception; our results suggest that this was partly caused by their knowing they belonged to a risk group and partly by their having experienced the disease at close range. Although family history positives had higher risk perceptions, no differences in early detection behavior were found. This could not be attributed to high anxiety levels. Implications for health education are discussed.     

Model-based cold-start speed control scheme for spark ignition engines

This paper presents a model-based control scheme to the cold-start speed control in spark ignition (SI) engines. The multi-variable control algorithm is developed with the purpose of improving the transient performance of the starting engine speed: the control inputs are the fuel injection, the throttle and the spark advance (SA), while the engine speed and the air mass flow rate are the measured signals. The fuel injection is performed with a dual sampling rate system: the cycle-based fuel injection command is individually adjusted for each cylinder by using a TDC (top dead center)-based air charge estimation. The desired performance for speed regulation is achieved by using a coordinated control of SA and throttle operation. The speed error convergence of the closed loop system is proved for simplified, second-order model with a time-delay, and the robustness with respect to parameter uncertainties is investigated. The performance and the robustness with respect to modeling uncertainties of the proposed control scheme are tested using an industrial engine simulator with six cylinders.     

An adaptive learning regulator for uncertain minimum phase systems with undermodeled unknown exosystems

The design of an adaptive learning regulator is addressed for uncertain minimum phase linear systems (with known bounds, known upper bound on system order, known relative degree, known high frequency gain sign) and for unknown exosystems (with unknown order, uncertain frequencies). On the basis of a known bound on system uncertainties and a known bound on the modeled exosystem frequencies, a new adaptive output error feedback control algorithm is proposed which guarantees exponential convergence of both the output and the control input errors into residual bounds which decrease as the exosystem modeling error decreases. Exponential convergence of both errors to zero is obtained when the regulator exactly models all exosystem excited frequencies, while asymptotic convergence of both errors to zero is achieved when the actual exosystem is overmodeled by the regulator. The new algorithm generalizes existing learning controllers since, in the case of periodic references and/or disturbances, the knowledge of the period is not required.     

Development of clinical indicators for performance measurement and improvement: an HMO/purchaser collaborative effort

This article describes a collaborative effort between a major health care purchaser, three area health maintenance organizations, and a state Medicaid agency to develop clinical indicators as the basis for a comparison database. Some of the difficulties in developing a "common yardstick" of quality and value are candidly discussed.     

Glass-fibre-reinforced composites with enhanced mechanical and electrical properties - Benefits and limitations of a nanoparticle modified matrix

Nanoparticles and especially carbon nanotubes (CNTs) provide a high potential for the modification of polymers. They are very effective fillers regarding mechanical properties, especially toughness. Furthermore, they allow the implication of functional properties, which are connected to their electrical conductivity, into polymeric matrices. In the present paper, different nanoparticles, as fumed silica and carbon black, were used to optimise the epoxy matrix system of a glass-fibre-reinforced composite. Their nanometre-size enables their application as particle-reinforcement in FRPs produced by the resin-transfer-moulding method (RTM), without being filtered by the glass-fibre bundles. Additionally, an electrical field was applied during curing, in order to enhance orientation of the nanofillers in z-direction. The interlaminar shear strengths of the nanoparticle modified composites were significantly improved (+16%) by adding only 0.3 wt.% of CNTs. The interlaminar toughness G_Ic and G_IIc was not affected in a comparable manner. The laminates containing carbon nanotubes exhibited a relatively high electrical conductivity at very low filler contents, which allows the implication of functional properties, such as stress-strain monitoring and damage detection.     

Adaptive control of linear time-varying systems

Single-input single-output uncertain linear time-varying systems are considered, which are affected by unknown bounded additive disturbances; the uncertain time-varying parameters are required to be smooth and bounded but are neither required to be sufficiently slow nor to have known bounds. The output, which is the only measured variable, is required to track a given smooth bounded reference trajectory. The undisturbed system is assumed to be minimum-phase and to have known and constant relative degree, known sign of the ‘high frequency gain’, known upper bound on the system order. An adaptive output feedback control algorithm is designed which assures: (i) boundedness of all closed-loop signals; (ii) arbitrarily improved transient performance of the tracking error; (iii) asymptotically vanishing tracking error when parameter time derivatives are L₁ signals and disturbances are L₂ signals.     

Photorefractive gratings in DR1-doped hybrid sol–gel films

Photorefractive gratings have been obtained with 632.8 nm writing beams in organic–inorganic SiO₂-based films. The hybrid glass is prepared by a sol–gel technique, starting from organic Si precursors, and contains Disperse Red 1 (DR1), carbazole units and 2,4,7-trinitro-9-fluorenone (TNF). The photorefractive gain, which has been found unexpectedly even without poling field, has been determined through an asymmetric energy exchange by two-beam coupling measurements. The effects of the polarization of the writing beams and of a circularly polarized photoisomerizing radiation during the erasure of the grating have been interpreted in terms of an orientational contribution to the grating formation.