Observation of Efficient Lower Hybrid Current Drive at High Density in Diverted Plasmas on the Alcator C-Mod Tokamak.

Efficient lower hybrid current drive (LHCD) is demonstrated at densities up to n[over ¯]_{e}≈1.5×10^{20} m^{-3} in diverted plasmas on the Alcator C-Mod tokamak by operating at increased plasma current-and therefore reduced Greenwald density fraction. This density exceeds the nominal "LH density limit" at n[over ¯]_{e}≈1.0×10^{20} m^{-3} reported previously, above which an anomalous loss of current drive efficiency was observed. The recovery of current drive efficiency to a level consistent with engineering scalings is correlated with a reduction in density shoulders and turbulence levels in the far scrape-off layer. Concurrently, rf wave interaction with the edge and/or scrape-off-layer plasma is reduced, as indicated by a minimal broadening of the wave frequency spectrum measured at the plasma edge. These results have important implications for sustaining steady-state tokamak operation and indicate a pathway forward for implementing efficient LHCD in a reactor.

Effects of magnetic shear on toroidal rotation in tokamak plasmas with lower hybrid current drive.

Application of lower hybrid (LH) current drive in tokamak plasmas can induce both co- and countercurrent directed changes in toroidal rotation, depending on the core q profile. For discharges with q(0) <1, rotation increments in the countercurrent direction are observed. If the LH-driven current is sufficient to suppress sawteeth and increase q(0) above unity, the core toroidal rotation change is in the cocurrent direction. This change in sign of the rotation increment is consistent with a change in sign of the residual stress (the divergence of which constitutes an intrinsic torque that drives the flow) through its dependence on magnetic shear.

Diagnostic development for parallel wave-number measurement of lower hybrid waves in EAST.

An eight-channel magnetic probe diagnostic system has been designed and installed adjacent to the 4.6 GHz lower hybrid (LH) grill antenna in the low-field side of the Experimental Advanced Superconducting Tokamak (EAST) in order to study the n∥ evolution of LH waves in the first pass from the launcher to the core plasma. The magnetic probes are separated by 6.6 mm, which allows measurement of the dominant parallel refractive index n∥ up to n∥ = 5 for 4.6 GHz LH waves. The magnetic probes are designed to be sensitive to the magnetic field component perpendicular to the background magnetic field with a slit on the casing that encloses the probe. The intermediate frequency stage, which consists of two mixing stages, down-coverts the frequency of the measured wave signals at 4.6 GHz to 20 MHz. A bench test demonstrates the phase stability of the magnetic probe diagnostic system. By evaluating the phase variation of the measured signals along the background magnetic field, the dominant n∥ of the LH wave in the scrape-off layer has been deduced during the 2019 experimental campaign. In the low density plasma, the measured dominant n∥ of the LH waves is about 2.1, corresponding to the main peak 2.04 of the launched n∥ spectrum. n∥ deduced by the least-squares linear fit method remains near this value in the low density plasma with a high spatial correlation magnitude of 0.9. With an eight-channel probe system, a wave-number spectrum has also been deduced, which has a peak near to the measured dominant n∥.

A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5.

Patients with hereditary haemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu syndrome) have variable presentation patterns and a high risk of preventable complications. Diagnostic tests for mutations in endoglin (HHT type 1) and ALK-1 (HHT type 2) are available. Some HHT patients are now known to have HHT-juvenile polyposis overlap syndrome due to Smad4 mutations. Families were ascertained following the presentation of probands for embolization of pulmonary arteriovenous malformations. Genome-wide linkage studies using over 700 polymorphic markers, and sequencing of candidate genes, were performed. In a previously described HHT family unlinked to endoglin or ALK-1, linkage to Smad4 was excluded, and no mutations were identified in the endoglin, ALK-1, or Smad4 genes. Two point LOD scores and recombination mapping identified a 5.4 cM HHT3 disease gene interval on chromosome 5 in which a single haplotype was inherited by all affected members of the pedigree. The remainder of the genome was excluded to a 2-5 cM resolution. We are currently studying a further family potentially linked to HHT3. We conclude that classical HHT with pulmonary involvement can result from mutations in an unidentified gene on chromosome 5. Identification of HHT3 should further illuminate HHT pathogenic mechanisms in which aberrant transforming growth factor (TGF)-beta signalling is implicated.

Horse rug lung: toxic pneumonitis due to fluorocarbon inhalation.

Fluorocarbons are widely used in industry, and manifestations of inhalation toxicity include polymer fume fever, reactive airways dysfunction, and bronchospasm. Only seven cases of alveolitis occurring acutely after inhalation have been reported. This paper presents four cases of toxic pneumonitis due to direct inhalation of industrial fluorocarbon used as a waterproofing spray for horse rugs. These cases differ from previous reports and show that chronic as well as acute alveolitis can result from fluorocarbon inhalation. Corticosteroid treatment may be beneficial. The need for stricter control in the workplace is emphasised.

Chest X-rays in COPD screening: are they worthwhile?

The BTS/NICE COPD guideline recommends a chest X-ray at initial COPD evaluation; this is a grade D recommendation based on expert opinion. We have investigated which pathologies other than COPD are detected by chest X-ray and how they alter management. Dundee smokers aged 40 or over and receiving bronchodilators are assessed for COPD by their practice nurse and offered a chest X-ray if there is no record of a chest X-ray within the previous three years. We retrospectively analysed the chest X-ray reports and case records of these patients. The chest X-ray report was structured with 7 specific questions, most importantly "Are there any features of other disease likely to be causing dyspnoea?" and "Are there any features to suggest lung cancer?" Management of patients with chest X-ray findings suggesting other disease causing dyspnoea or lung cancer was assessed by questionnaire and case record study. Five hundred forty-six consecutive chest X-ray reports were analysed. Fourteen percent of all chest X-rays detected potentially treatable dyspnoea causing disease; where management following receipt of X-ray reports was audited, 84% were thought to help. Eleven lung cancers were detected, 3 had stage 1 disease. Considerable benign and malignant pathology is detected by chest X-ray performed at initial COPD assessment. Clinical management is changed in the majority with a potentially treatable abnormality. This evidence suggests that the NICE guideline to perform chest X-ray at initial COPD evaluation should be elevated from a grade D to grade C recommendation.

Scrape-off layer reflectometer for Alcator C-Mod.

A two-frequency x-mode reflectometer operating from 100 to 146 GHz is deployed on Alcator C-Mod to measure the density profile and fluctuations in the scrape-off layer (SOL) immediately in front of the new J-port ICRF antenna and the new C-port lower hybrid launcher. The reflectometer covers densities from 10(16) to 10(20) m(-3) at 5-5.4 T. To provide the greatest flexibility and capability to deal with density fluctuations approaching 100% peak-to-peak in the SOL, both full-phase and differential-phase measurement capabilities with sweep speeds of approximately 10 micros to >1 ms are implemented. The differential-phase measurement uses a difference frequency of 500 MHz, corresponding to cutoff layer separations ranging from about 0.1 to 1 mm. The reflectometer has six sets of launchers: three on the ICRF antenna and three on the lower hybrid launcher. Both the ICRF antenna and the lower hybrid launcher incorporate reflectometer antennas at their top, bottom, and midplane locations.

A hereditary haemorrhagic telangiectasia family with pulmonary involvement is unlinked to the known HHT genes, endoglin and ALK-1.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) occur in over 25% of patients with the autosomal dominant disorder hereditary haemorrhagic telangiectasia (HHT). Mutations in two genes, endoglin and ALK-1, are known to cause HHT. Each encodes a protein expressed on vascular endothelial cells and involved in signalling by members of the transforming growth factor (TGF)-beta superfamily. To date, PAVMs have not been detected in ALK-1 families. There is evidence from a single HHT family without pulmonary involvement that a third HHT gene may exist. To establish the existence of a further HHT gene responsible for PAVMs, linkage analyses were performed on an expanded PAVM-HHT family in which HHT did not result from endoglin mutations. METHODS: Family members were assessed clinically to assign HHT disease status and were screened for PAVMs. DNA was extracted from blood obtained from 20 individuals of known disease status. Short tandem repeat polymorphic markers spanning the intervals containing the endoglin and ALK-1 genes were amplified by the polymerase chain reaction using (33)P-labelled oligonucleotide primers, separated by denaturing polyacrylamide gel electrophoresis (PAGE), and the resultant autoradiographs were examined for allele sizes. Linkage analyses were performed using MLINK and GENEHUNTER. RESULTS: Twelve members spanning four generations were affected with HHT. Two had proven PAVMs, one with a classical appearance, the other exhibiting microscopic PAVMs exacerbated by pregnancy. Two point lod and multipoint lod scores significantly excluded linkage to endoglin and ALK-1 in this pedigree. CONCLUSIONS: This study confirms the existence of a third HHT locus that accounts for disease in some HHT patients with pulmonary involvement.

The effects of dietary deprivation on body temperature and oxygen consumption in black-tailed prairie dogs (Cynomys ludovicianus).

1. Body temperature (Tb) and oxygen consumption (VO2) were compared between fed (Control), food and water deprived (FWD), and water deprived (WD) black-tailed prairie dogs, in the month of January. 2. Mean Tb of Control black-tailed prairie dogs (36.2 degrees C) was significantly different from FWD (33.4 degrees C) and WD (30.4 degrees C) black-tailed prairie dogs. 3. VO2 was not significantly different between FWD and Control black-tailed prairie dogs (4.4 and 4.0 ml O2/kg/hr, respectively), while VO2 was significantly different between WD and Control animals (2.9 and 4.0 ml O2/kg/hr, respectively). 4. These findings are discussed as possible mechanisms for conserving body water.

Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century.

Hereditary haemorrhagic telangiectasia (HHT) affects one in 5-8000, and no longer can be viewed as solely causing anaemia (due to nasal and gastrointestinal bleeding) and characteristic mucocutaneous telangiectasia. Arteriovenous malformations commonly occur, and in the pulmonary and cerebral circulations demand knowledge of risks and benefits of asymptomatic screening and treatment. HHT is inherited as an autosomal dominant trait and there is no age cut off when apparently unaffected offspring of an individual with HHT can be told they are unaffected. This review focuses on the evolving evidence base for HHT management, issues regarding pregnancy and prothrombotic treatments, and discusses the molecular and cellular changes that underlie this disease.

Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22,061 years of HHT patient life.

BACKGROUND: The frequency of haemorrhage in individuals with hereditary haemorrhagic telangiectasia (HHT), 10% of whom will have cerebral arteriovenous (AV) malformations, could be high enough to justify screening. This would allow presymptomatic treatment to prevent early onset stroke in a condition that affects at least 1 in 8000 individuals. This is an important issue in view of the contrast between transatlantic management approaches, the worldwide dissemination of patient information, and the ethical implications of the diagnosis for the untreated patient. OBJECTIVES: To define the annual incidence of haemorrhagic stroke in individuals with HHT. METHODS: Retrospective study on stroke incidence in individuals with HHT and their immediate families (n = 674; 22,061 HHT patient years), specifically analysing patients under 46 years of age (17,515 patient years). The results were compared with stroke risk in the general population. RESULTS: In the majority of cases, the haemorrhage was the first significant neurological event. Overcorrecting for any bias towards overestimation that would be introduced in excluding non-penetrant family members, cerebral haemorrhages were more than 20 times more common in male HHT subjects under the age of 45 years than in the general population (standardised ratio 22.99; 95% confidence interval, 13.14 to 37.33). Haemorrhages were also six times more common in female HHT subjects (6.18; 2.27 to 13.45). The incidence ratio of cerebral haemorrhage in male patients (1.84; 1.05 to 2.99) yielded a haemorrhage rate in individuals with cerebral AV malformations of 1.4-2.0% per annum, comparable to figures in the non-HHT cerebral AV malformation population. CONCLUSIONS: These data contradict accepted wisdom in many countries that asymptomatic HHT patients are at a low (and acceptable) risk of haemorrhage. The data justify a more aggressive screening approach to identify small causative lesions amenable to treatment.