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Background: Cognitive impairment (CI) is common in Parkinson’s disease (PD) and an important cause of disability. Screening facilitates early detection of CI and has implications for management. Preclinical disability is when patients have functional limitations but maintain independence through compensatory measures. Objective: The objective of this study was to investigate the relationship between scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) with levels of PD severity and disability. Methods: PD patients (n = 2,234) in a large observational study were stratified by disease severity, based on Total Unified Parkinson’s Disease Rating Scale (Total UPDRS) and Hoehn and Yahr (HY) stage. Using MMSE (n = 1,184) or MoCA (n = 1,050) and basic (ADL) and instrumental activities of daily living (IADL) scales for disability, linear regression analysis examined associations between cognitive status and disability. Results: Cognition and disability were highly correlated, with the strongest correlation between IADL and MoCA. Only 16.0% of mean MMSE scores were below threshold for CI (28) and only in advanced PD (Total UPDRS 60+, HY≥3). MoCA scores fell below CI threshold (26) in 66.2% of the sample and earlier in disease (Total UPDRS 30+, HY≥2), corresponding with impairments in ADLs. Conclusion: In a large clinical dataset, a small fraction of MMSE scores fell below cutoff for CI, reinforcing that MMSE is an insensitive screening tool in PD. MoCA scores indicated CI earlier in disease and coincided with disability. This study shows that MoCA, but not MMSE is sensitive to the emergence of early cognitive impairment in PD and correlates with the concomitant onset of disability.

Objective To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. Methods In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. Results Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. Conclusion These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

The influence of methylprednisolone on the migratory characteristics of neutrophil granulocytes was investigated in 10 patients with early rheumatoid arthritis (RA) and compared to 12 controls. The migration of neutrophils was measured with a whole-blood membrane filter assay with and without stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Total migration index (TMI), distribution characteristics (DC) and the product of TMI and DC (neutrophil migratory activity; NMA) served to characterize the migratory behaviour of neutrophils. The data demonstrated an increased polymorphonuclear leucocyte (PMN) migration in patients with early RA, indicating a bystander role of PMNs in inflammatory joint injury. Treatment with methylprednisolone reduced significantly the penetration depth (DC) of neutrophils, but did not influence the number of migrating cells (TMI). The unstimulated NMA was significantly reduced due to the marked DC reduction, whereas steroids did not influence the stimulated NMA of neutrophils. A significant reduction in PMN penetration depth was demonstrated only after a steroid therapy of at least 10 days, suggesting that a longer period of steroid therapy is necessary to provide effective inflammatory control.

Relapsing polychondritis (RP) is a relatively rare disorder, with a high death rate that affects cartilaginous structures. RP can be either primary or secondary as part of autoimmune syndromes. We present a case of RP in a 49-year-old man suffering from cytoplasmic antineurophil cytoplasmic antibodies (cANCA) positive vasculitis, admitted to our hospital with red swollen left ear and painful sternoclavicular joint and larynx. The patient was in remission from the vasculitis but manifested a high cANCA titre indicating vasculitis activity. With his high cANCA titre vasculitis, full manifestation of RP concomitantly occurred. After a successful cortisone treatment for RP, the patient received cyclophosphamide treatment for his vasculitis that resulted in a decrease in cANCA titre and full remission of his RP symptoms.

Several low-Z refractory materials are evaluated for use as the NIF first wall in terms of their cost and ability to survive laser light, target emissions and debris, as well as be cleanable and not outgas excessively. Best performers contain B, C, or both, with B{sub 4}C being the best overall. It appears possible at this time that plasma-sprayed B{sub 4}C can be fabricated with low enough porosity and cost to be preferred to hot-pressed B{sub 4}C, the conservative choice.

Blood polymorphonuclear leukocyte (PMN) migratory activity was investigated in adult rheumatoid arthritis (RA) patients and in healthy control subjects using fresh whole blood in a novel membrane filter assay. The PMNs migrated under FMLP stimulation and under blank control conditions (spontaneous migration). Essential evaluation criteria were the percentage of PMNs that migrated from the entire blood sample into the filters (TMI) and the penetration depth of the migrating cell bulk into the filters (DC). PMNs from healthy subjects penetrate deeper under FMLP stimulation than under blank control conditions. Migration depends on age and sex: the TMI decreases, while the DC and the reactivity towards FMLP increase with age. FMLP triggers a stronger DC reaction in females than in males. Compared with healthy subjects, patients with RA develop an increased PMN reaction, whereas FMLP inhibits migration in comparison with the blank controls. There is no correlation between disease activity estimated by joint functions and PMN migratory activity, while there are strong correlations between disease activity and the classical RA laboratory parameters WBC, platelets, BSR, CRP, hemoglobin and rheumatoid factor. PMNs therefore probably do not play a major role in joint injury. Gold therapy inhibits DC reactivity. PMN migration in RA differs markedly from the reactions in juvenile rheumatoid arthritis, where high disease activity is associated with high PMN migratory activity, and the correlations between classical laboratory parameters and disease activity follow other patterns than in RA.

Examples of imagery from experimental oil spills in the North Sea during August 1993 are presented to illustrate how remote sensing imagery, if integrated into spill management systems, can affect the decision making process. Time series data from multiple sensor types can be processed and interpreted from a response perspective using new spatial data management and imaging software to aid emergency response efforts. Until now, remote sensing platforms for oil spills, despite substantial records of past use, have been used as little more than spotter aircraft that supplemented reports from an observer with a camera and sketchpad. With the integration of image processing technology, multiple sensors and aircraft avionics, spill surveillance, usually limited to descriptions about the general size and approximate location of a patch of oil, can now provide quantitative information about the physical aspects of an entire spill and an understanding of its behavior over time, within the environment surrounding the spill. The ability to detect and measure changes relating to the characteristics of a spill itself, as well as the surrounding environment, marks the beginning for new commercial opportunities and applications of remote sensing technology—oil spill detection being just one example. Further, it demonstrates how management decisions, emergency response and strategic planning needs will be supported in coming years.

A transition is underway in imaging technology for airborne surveillance and reconnaissance operations. Large independent sensor systems carried in dedicated airframes, are being replaced by more economical, compact, and integrated multisensor arrays with a common processor that are portable enough to fit into a variety of small aircraft. Development of such a system was stimulated by a perceived need to enhance marine oil spill response and cleanup, and to better mitigate the environmental and economic impact of such incidents. The newest of these systems incorporates an aerial platform, a suite of advanced commercial sensors, a six degrees of freedom global positioning system (GPS), advanced database technology to manage spatial data, and image analysis capabilities. The operational goal of this development is to furnish valuable reconnaissance information in real time to ground users. Such a capability could advance oil spill response and other applications where rapid acquisition, integration, and communication of complex data is essential to decision-making. The ability to conduct day, night, and adverse weather surveillance operations is restricted in current systems and is another benefit this system is designed to provide. The innovation in the system especially lies in the development of a common processor and image fusion system which integrates, georeferences, and geocorrects multisensor data and transmits it in real time. A graphic interface was designed to provide maps or other projections as a spatial reference system on which to plot data from a surveillance mission. New imaging numerical methods allow processing of composite images, multi-image mosaics, change detection, and other data manipulation, and were tested in field trials of the system.

A 2-week multicentre, double-blind, randomised trial was conducted to evaluate the efficacy and tolerability of diclof enac resinate, a new galenic formulation of diclofenac, versus piroxicam, an established analgesic/anti-inflammatory agent, in patients suffering from acute lumbosacral back pain. Adult male or female patients complaining of moderate to severe pain at rest/on movement were treated with either diclofenac resinate 75mg twice daily or piroxicam 20mg once daily for up to 14 days; the latter group received piroxicam 40 mg/day for the first 2 days. In the 132 patients eligible for efficacy analyses (66 in each treatment group), both drugs led to comparable and clinically significant reductions in mean pain scores commencing after 3 days of treatment. Tests for spinal flexion also showed considerable improvement, as did functional capability, with no significant differences being observed between diclofenac and piroxicam. Overall evaluations of efficacy by the investigators and the patients revealed a positive response rate in 78.8 and 81.8%, respectively, in patients treated with diclofenac compared with 83.3 and 87.7%, respectively, for piroxicam. The incidence of adverse effects, most frequently gastrointestinal, was 19.7% for diclofenac resinate and 18.2% for piroxicam. The results of this controlled study show that diclofenac at a daily dosage of 150mg has efficacy similar to piroxicam 20mg with a loading dose regimen of 40mg for the symptomatic management of acute lumbosacral back pain.

Sternoclavicular septic arthritis is a rare complication of subclavian venous catheterization. We estimate that septic involvement of this joint may be as common as one in 500 catheterizations. We report two patients with insidious onset of shoulder pain, chest discomfort, low-grade fever and slight but painful swelling of a sternoclavicular joint four weeks following subclavian venous catheterization. Positive blood cultures in the presence of abnormal bone scan and abnormal conventional X-ray examination or computed tomography of the sternoclavicular joint led to the diagnosis of septic arthritis. Both patients responded well to antibiotic treatment. Based on our observations and that reported in the literature, the earliest changes of sternoclavicular septic arthritis may be detected by bone scan while plain X-ray studies and CT become abnormal during advanced stages of this type of arthritis. We would like to alert physicians to this cause of fever and joint pain in patients who previously underwent subclavian venous catheterization.

SUMMARY One hundred and seventy-three consecutive patients with rheumatoid arthritis were examined for the presence of anticardiolipin antibodies (ACA), and for the clinical relevance and the relation of these antibodies to skin manifestations. Abnormally elevated IgG- and/or IgM-ACA levels were detected by an enzyme-linked immunosorbent assay in the sera of 55 (32%) patients. There was no statistical evidence of an association between ACA and a history of thrombosis in these patients. However, ACA were statistically significantly linked to the presence of rheumatoid nodules, which were found in 36 (21%) patients. In three patients, ACA were associated with vascular manifestations, including livedo reticularis, thrombophlebitis, and leucocytoclastic vasculitis. Our findings suggest that, although a subset of ACA may be linked to cutaneous vascular conditions, the major fraction of ACA in rheumatoid arthritis may have a different specificity than in other diseases, in which ACA are often linked to thrombotic events.

The detection of calcium pyrophosphate dihydrate (CPPD) crystals is more difficult than that of monosodium urate (MSU) crystals because of their small and varying size and frequently low concentrat...

The research and development program of the Marine Spill Response Corporation is solidly under way in a variety of project areas. These include remote sensing, in-situ burning, dispersants, oil/water separation, countermeasures effectiveness, bioremediation, and evaluation of spill effects. More than thirty projects have been contracted. Among these are remote sensing studies, which started with in-depth market analyses, technical feasibility evaluations, and field studies. The remote sensing program is engaged in rapid development of a research test bed system, as well as longer-term studies on sensor development and use of satellite systems. In-situ burning studies included a detailed analysis of operational feasibility and information needs; preparations are being made for test burns at sea and improvements of fire-resistant barrier systems. Studies are underway on both aerial dispersant application system development and dispersant effects in selected environments. Studies have commenced on the development of oil/water separators for vessels of opportunity used in oil spill response, as well as the related issue of demulsification. The effectiveness of spill countermeasures is being investigated from both engineering and ecological perspectives. Bioremediation projects are under way to promote the development of test systems and on shoreline test sites. Interest continues in test spills in the marine environment, including participation in experimental spills outside the United States and a search for possible scenarios where such field experiments can be carried out in United States waters. In all of these project areas, the research and development program stresses information transfer by way of meetings and publications, and is initiating publication of a peer reviewed international journal on oil spill science and technology. Working collaboration with other organizations at federal and state levels, as well as internationally, has been established under a variety of agreements and understandings for research and development cooperation.

A series of 4-layer silica-tantala antireflection coatings was deposited under 18 different combinations of substrate temperature (175, 250, and 325 degrees C), oxygen pressure (0.5,1.0, and 2.0 x 10(-4) Torr), and rate of deposition (1.5 and 5 A/sec). Measurements of laser-damage threshold for 1064-nm, 1-nsec pulses, average absorption, net stress, and reflectivity were then made on these coatings. Coatings deposited at the lowest temperature had the highest damage thresholds. Damage thresholds were found not to be directly related to average absorption or net stress. Coatings deposited on fused silica substrates which had been polished by a bowl-feed process had generally higher damage thresholds than coatings deposited on conventionally polished fused silica or on BK-7 glass polished by either conventional or bowl-feed processes. Baking coatings in air for 4 h at 400 degrees C generally reduced average absorption and net stress, changed the net stress from compression to tension and, in some cases, increased the damage threshold.

Interferometric measurements have been made of the optical distortions induced in laser disk amplifiers during the flashlamp pumping pulse. Both conventional interferometric methods and the techniques of double exposure holographic interferometry were used to identify four major sources of pump-induced optical distortions: subsonic intrusion of hot gas (traced to leakage of atmospheric oxygen into the amplifier), microexplosions of dust particles, thermally induced optical distortions in the glass disks, and gaseous optical distortion effects caused by turbulent flow of the purging nitrogen gas supply used within the laser amplifier head. Methods for reducing or eliminating the effects of each of these optical distortions are described.

We have measured the laser-induced damage thresholds for 248 nm wavelength light of over 100 optical coatings from commercial vendors and research institutions. All samples were irradiated once per damage site with temporally multi-lobed, 20-ns pulses generated by a KrF laser. The survey included high, partial, and dichroic reflectors, anti-reflective coatings, and single layer films. The samples were supplied by ten vendors. The majority of samples tested were high reflectors and antireflective coatings. The highest damage thresholds were 8.5 to 9.4 J/cm/sup 2/, respectively. Although these represent extremes of what has been tested so far, several vendors have produced coatings of both types with thresholds which consistently exceed 6 J/cm/sup 2/. Repeated irradiations of some sites were made on a few samples. These yielded no degradation in threshold, but in fact some improvement in damage resistance. These same samples also exhibited no change in threshold after being retested seven months later.

Isolated bulk damage centers are produced when KDP crystals are irradiated by 1-ns 1064-nm pulses. We have tested about 100 samples and find the median threshold to be 7 J/cm/sup 2/ when the samples are irradiated only once at each test volume (1-on-1 tests). The median threshold increased to 11 J/cm/sup 2/ when the test volumes were first subjected to subthreshold laser irradiation (n-on-1 tests). We baked several crystals at temperatures from 110 to 165/sup 0/C and remeasured their thresholds. Baking increased thresholds in some crystals, but did not change thresholds of others. The median threshold of baked crystals ranged from 8 to 10 J/cm/sup 2/ depending on the baking temperature. In crystals that had been baked, subthreshold irradiation produced a large change in the bulk damage threshold, and reduced the volume density of damage centers relative to the density observed in unbaked crystals. The data are summarized in the table.

We have conducted an extensive series of laser damage measurements on highly reflective (HR) dielectric coatings which have yielded 1064-nm thresholds as high as 40 J/cm for 8to 10-ns pulses at pulse-repetition frequencies (PRF) of 10 Hz. Moreover, by laser conditioning these coatings with subthreshold pulses, the thresholds of some coatings were raised to levels exceeding 70 J/cm. These are the highest threshold dielectric HR coatings that we have tested in this regime. The coatings were originally developed to produce HR-overcoated metal mirrors for free-electronlaser (EEL) app1icationsat high PRF. Our tests included coatings deposited on both dielectric substrates and molybdenum (Mo) substrates. In each category we also examined coatings with a pre-coat of Mo between the substrate and the HR stack. The improved dielectric HR stacks effectively shielded the Mo from the laser irradiation so that the thresholds of virtually all Mo samples exceeded levels of the best dielectric-enhanced and dielectric-HR-coated metal mirrors we have tested to date. In addition to the low PRF measurements, we also conducted 1064-nm damage tests at 6-kHz PRF using 65-ns pulses from the Kilroy damage test facility. The coatings survived thermal loading of fluences ranging from 2 to 10 J/cm2 with respective small spot sizes on the order of 1 .2 to 0.3 mm (1 /e? diameter).

Recently, we have expanded our efforts to develop state-of-the-art optical components for use in large-scale, high-peak-power, solid state lasers. Laser-induced damage to many of these components sets critical constraints on construction costs and limits the peak powers attainable in current and proposed devices. Increasing the damage threshold whenever possible by improving materials fabrication technology is therefore the ultimate goal of our work. Our research has resulted in an extensive database of laser-damage measurements. We present summaries of these measurements with particular emphasis on those taken at 1064 nm and 355 nm.

Multilayer dielectric optical coatings, nominally consisting of 1000 or more optical-quarterwave layers, have been prepared by reacting SiCl{sub 4} and a halogenated dopant (e.g. GeCl{sub 4}) with O{sub 2} in a microwave-driven plasma. The dopant concentration is such that the index difference ({Delta}n) between adjacent quarterwave layers is about 0.02 or less. The deposition is carried out at high substrate temperatures (850 to 1100{degree}C) producing a fully dense, fused silica coating. Surface damage thresholds of high reflectivity (HR) coatings prepared by this plasma process are comparable to those for fused silica. For example, at 1.06 {mu}m and 16-ns we measure surface damage thresholds greater than 45 J/cm{sup 2} compared to about 45--60 G/cm{sup 2} for super-polished optical fused silica. 25 refs., 12 figs., 1 tab.