Four-dimensional (4D) tracking of high-temperature microparticles.

High-speed tracking of hot and molten microparticles in motion provides rich information about burning plasmas in magnetic fusion. An exploding-wire apparatus is used to produce moving high-temperature metallic microparticles and to develop four-dimensional (4D) or time-resolved 3D particle tracking techniques. The pinhole camera model and algorithms developed for computer vision are used for scene calibration and 4D reconstructions. 3D positions and velocities are then derived for different microparticles. Velocity resolution approaches 0.1 m/s by using the local constant velocity approximation.

Phase-locking of magnetic islands diagnosed by ECE-imaging.

Millimeter-wave imaging diagnostics identify phase-locking and the satisfaction of 3-wave coupling selection criteria among multiple magnetic island chains by providing a localized, internal measurement of the 2D power spectral density, S(ω, kpol). In high-confinement tokamak discharges, these interactions impact both plasma rotation and tearing stability. Nonlinear coupling among neoclassical tearing modes of different n-number, with islands not satisfying the poloidal mode number selection criterion ⟨m, m('), m - m(')⟩, contributes to a reduction in core rotation and flow shear in the vicinity of the modes.

Commissioning of electron cyclotron emission imaging instrument on the DIII-D tokamak and first data.

A new electron cyclotron emission imaging diagnostic has been commissioned on the DIII-D tokamak. Dual detector arrays provide simultaneous two-dimensional images of T(e) fluctuations over radially distinct and reconfigurable regions, each with both vertical and radial zoom capability. A total of 320 (20 vertical×16 radial) channels are available. First data from this diagnostic demonstrate the acquisition of coherent electron temperature fluctuations as low as 0.1% with excellent clarity and spatial resolution. Details of the diagnostic features and capabilities are presented.

2D electron cyclotron emission imaging at ASDEX Upgrade (invited).

The newly installed electron cyclotron emission imaging diagnostic on ASDEX Upgrade provides measurements of the 2D electron temperature dynamics with high spatial and temporal resolution. An overview of the technical and experimental properties of the system is presented. These properties are illustrated by the measurements of the edge localized mode and the reversed shear Alfvén eigenmode, showing both the advantage of having a two-dimensional (2D) measurement, as well as some of the limitations of electron cyclotron emission measurements. Furthermore, the application of singular value decomposition as a powerful tool for analyzing and filtering 2D data is presented.

Advancements in electron cyclotron emission imaging demonstrated by the TEXTOR ECEI diagnostic upgrade.

A new TEXTOR electron cyclotron emission imaging system has been developed and employed, providing a diagnostic with new features and enhanced capabilities when compared to the legacy system it replaces. Optical coupling to the plasma has been completely redesigned, making use of new minilens arrays for reduced optical aberration and providing the new feature of vertical zoom, whereby the vertical coverage is now remotely adjustable on a shot-by-shot basis from 20-35 cm. Other innovations, such as the implementation of stacked quasioptical planar notch filters, allow for the diagnostic to be operated without interruption or degradation in performance during electron cyclotron resonance heating. Successful commissioning of the new diagnostic and a demonstration of the improved capabilities are presented in this paper, along with a discussion of the new technologies employed.

Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.

Observation of high-field-side crash and heat transfer during sawtooth oscillation in magnetically confined plasmas.

High resolution (temporal and spatial), two-dimensional images of electron temperature fluctuations during sawtooth oscillations were employed to study the crash process and heat transfer in magnetically confined toroidal plasmas. The combination of kink and local pressure driven instabilities leads to a small poloidally localized puncture in the magnetic surface at both the low and the high field sides of the poloidal plane. This observation closely resembles the "fingering event" of the ballooning mode model with the high- mode only predicted at the low field side.

Comparison study of 2D images of temperature fluctuations during sawtooth oscillation with theoretical models.

High temporal and spatial resolution two-dimensional (2D) images of electron temperature fluctuations were employed to study the sawtooth oscillation in the Toroidal Experiment for Technically Oriented Research tokamak plasmas. The 2D images are directly compared with the expected 2D patterns of the plasma pressure (or electron temperature) from various theoretical models. The observed experimental 2D images are only partially in agreement with the expected patterns from each model: The image of the initial reconnection process is similar to that of the ballooning mode model. The intermediate and final stages of the reconnection process resemble those of the full reconnection model. The time evolution of the images of the hot spot or island is partially consistent to those from the full reconnection model but is not consistent with those from the quasi-interchange model.

Lead exposure as a risk factor for amyotrophic lateral sclerosis.

BACKGROUND: The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to >4-fold. However, these results may have been affected by recall bias. OBJECTIVE: To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead. METHODS: We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure. RESULTS: In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each mug/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk. CONCLUSION: These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease.

Controlled optimization of mode conversion from electron Bernstein waves to extraordinary mode in magnetized plasma.

In the CDX-U spherical torus, agreement between radiation temperature and Thomson scattering electron temperature profiles indicates approximately 100% conversion of thermally emitted electron Bernstein waves to the X mode. This has been achieved by controlling the electron density scale length (L(n)) in the conversion region with a local limiter outside the last closed flux surface, shortening L(n) to the theoretically required value for optimal conversion. From symmetry of the conversion process, prospects for efficient coupling in heating and current drive scenarios are strongly supported.

Slowing down ALS--is this good or bad?

The availability of a drug that provides modest relief in ALS without altering its inevitable progression and end, has posed new ethical and economic problems for patients, caregivers and physicians. Early evidence suggests that riluzole does provide a short additional quality of life and economic benefit for patient and society. However, there is a clear need for additional therapies, even if the benefit is minor.

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome.

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.

Dietary intake of calcium, magnesium and antioxidants in relation to risk of amyotrophic lateral sclerosis.

Dietary factors have long been suspected of being risk factors for amyotrophic lateral sclerosis (ALS), but few human studies have been reported. To address several of the dietary hypotheses, a case-control study of risk factors for ALS conducted in New England in 1993-1996 included an abbreviated food frequency questionnaire. We examined the dietary intake of calcium, magnesium and antioxidants among 107 ALS cases and 262 community controls. Overall, these dietary factors were not related to risk of ALS, though modestly protective associations were suggested for magnesium and lycopene.

The global burden of disease study: implications for neurology.

Because of the epidemiological transition, the global burden of illness has changed. Several factors have contributed to this change, including improvements in maternal and child health, increasing age of populations, and newly recognized disorders of the nervous system. It is now evident that neurologic disorders have emerged as priority health problems worldwide. This is reflected in the Global Burden of Disease Study, jointly published by the World Health Organization and other groups. The proportionate share of the total global burden of disease resulting from neuropsychiatric disorders is projected to rise to 14.7% by 2020. Although neurologic and psychiatric disorders comprise only 1.4% of all deaths, they account for a remarkable 28% of all years of life lived with a disability. This study provides compelling evidence that one cannot assess the neurologic health status of a population by examining mortality statistics alone. Health ministries worldwide must prioritize neurologic disorders, and neurologists must be prepared to provide care for increased numbers of people individually and in population groups.

The ALS patient care database: goals, design, and early results. ALS C.A.R.E. Study Group.

OBJECTIVE: The ALS Patient Care Database was created to improve the quality of care for patients with ALS by 1) providing neurologists with data to evaluate and improve their practices, 2) publishing data on temporal trends in the care of patients with ALS, and 3) developing hypotheses to be tested during formal clinical trials. BACKGROUND: Substantial variations exist in managing ALS, but there has been no North American database to measure outcomes in ALS until now. METHODS: This observational database is open to all neurologists practicing in North America, who are encouraged to enroll both incident and prevalent ALS patients. Longitudinal data are collected at intervals of 3 to 6 months by using standard data collection instruments. Forms are submitted to a central data coordinating center, which mails quarterly reports to participating neurologists. RESULTS: Beginning in September 1996 through November 30, 1998, 1,857 patients were enrolled at 83 clinical sites. On enrollment, patients had a mean age of 58.6 years +/-12.9 (SD) years (range, 20.1 to 95.1 years), 92% were white, and 61% were men. The mean interval between onset of symptoms and diagnosis was 1.2+/-1.6 years (range, 0 to 31.9 years). Riluzole was the most frequently used disease-specific therapy (48%). Physical therapy was the most common nonpharmacologic intervention (45%). The primary caregiver was generally the spouse (77%). Advance directives were in place at the time of death for 70% of 213 enrolled patients who were reported to have died. CONCLUSIONS: The ALS Patient Care Database appears to provide valuable data on physician practices and patient-focused outcomes in ALS.

Consensus guidelines for the design and implementation of clinical trials in ALS. World Federation of Neurology committee on Research.

BACKGROUND: In 1994 consensus guidelines were developed for conducting clinical trials in ALS. With growing experience in clinical trials, it has become clear that a number of further guidelines were needed. METHODS: Under the auspices of the World Federation of Neurology Committee on Research, a multinational group of neurologists, statisticians, patient advocates, representatives from the pharmaceutical industry as well as regulatory agencies developed consensus about a number of revisions to the existing guidelines during a 2 day conference in April 1998. RESULTS: Expanded areas of focus include greater protection of patient rights, more detailed guidelines for outcome measures statistical analyses, disclosure of study results and improved interaction between investigators and the corporate sector. COMMENT: Substantial progress has been made in standardizing and improving the quality of clinical trials in ALS through these consensus guidelines.