Lava Flows Erupted in 1996 on North Gorda Ridge Segment and the Geology of the Nearby Sea Cliff Hydrothermal Vent Field From 1-M Resolution AUV Mapping

The northernmost segment of the Gorda mid-ocean ridge is the site of a small-volume eruption in 1996 and the persistent off-axis Sea Cliff hydrothermal vent field. To better understand the geologic setting and formation of these features, 1-m resolution bathymetric mapping using autonomous underwater vehicles was completed in 2016. The mapped region covers 35 km2 and 15.6 km of the volcanic axis from south of the 1996 lava flows, and a cross section for ∼4.5 km perpendicular to the axis, that extends beyond the Sea Cliff hydrothermal vent field. A proposed 1996 flow ∼7 km south of previously mapped flows is an artifact from a poor pre-eruption survey. The 1996 flows consist of three discrete steep hummocky mounds of pillows and syneruptive talus. The Sea Cliff hydrothermal field is located a few km north of the narrowest, shallowest section of the ridge segment, 2.6 km east of the center of the neovolcanic zone, and ∼370 m above the average depth of the axial graben on the largest offset ridge-parallel fault. No evidence supports the prior hypothesis that the site is located where two fault systems intersect. The axial graben is asymmetrical with larger fault offsets on the east side. The ridge axis below the hydrothermal field and to the south toward the 1996 flows is constructed dominantly of hummocky flows of pillow basalt, many unusually steep-sided, with syneruptive talus at the base of their steep slopes. Three channelized flows ponded between steep hummocky flows, and then partially drained. Some low-eruption-rate hummocky flows and high-eruption-rate channelized flows have nearly identical compositions, supporting the idea that eruption rates on mid-ocean ridges vary because of different dike widths. Four volcanic structures with volumes between 0.18 and 0.25 km3 occur in the axial graben south of the 1996 flows. Two are flat-topped cones, another is a 1.5-km diameter inflated hummocky flow with 7 pit craters that demonstrate that the flow had a molten interior during growth. The fourth voluminous structure is a steep ridge with abundant syneruptive talus on its lower slopes. The North Gorda segment is an end-member, structurally and volcanically, compared with other Pacific intermediate-rate spreading ridges

Efficacy and Safety of a New 20% Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in Patients With Primary Immunodeficiency

Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5–72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs

Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

Therapeutic Management of Primary Immunodeficiency in Older Patients

Primary immunodeficiency disease (PID) has traditionally been viewed as a group of illnesses seen in the paediatric age group. New advances in diagnosis and treatment have led to an increase in the number of elderly PID patients. However, there is lack of research evidence on which to base clinical management in this group of patients. Management decisions often have to be based therefore on extrapolations from other patient cohorts or from younger patients. Data from the European Society for Immunodeficiencies demonstrates that the vast majority of elderly patients suffer from predominantly antibody deficiency syndromes. We review the management of PID disease in the elderly, with a focus on antibody deficiency disease

Myasthenia gravis

Myasthenia gravis (MG) is a rare, autoimmune neuromuscular junction disorder. Contemporary prevalence rates approach 1/5,000. MG presents with painless, fluctuating, fatigable weakness involving specific muscle groups. Ocular weakness with asymmetric ptosis and binocular diplopia is the most typical initial presentation, while early or isolated oropharyngeal or limb weakness is less common. The course is variable, and most patients with initial ocular weakness develop bulbar or limb weakness within three years of initial symptom onset. MG results from antibody-mediated, T cell-dependent immunologic attack on the endplate region of the postsynaptic membrane. In patients with fatigable muscle weakness, the diagnosis of MG is supported by: 1. pharmacologic testing with edrophonium chloride that elicits unequivocal improvement in strength; 2. electrophysiologic testing with repetitive nerve stimulation (RNS) studies and/or single-fiber electromyography (SFEMG) that demonstrates a primary postsynaptic neuromuscular junctional disorder; and 3. serologic demonstration of acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies. Differential diagnosis includes congenital myasthenic syndromes, Lambert Eaton syndrome, botulism, organophosphate intoxication, mitochondrial disorders involving progressive external ophthalmoplegia, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), motor neuron disease, and brainstem ischemia. Treatment must be individualized, and may include symptomatic treatment with cholinesterase inhibitors and immune modulation with corticosteroids, azathioprine, cyclosporine, and mycophenolate mofetil. Rapid, temporary improvement may be achieved for myasthenic crises and exacerbations with plasma exchange (PEX) or intravenous immunoglobulin (IVIg). Owing to improved diagnostic testing, immunotherapy, and intensive care, the contemporary prognosis is favorable with less than five percent mortality and nearly normal life expectancy

Lava Flows Erupted in 1996 on North Gorda Ridge Segment and the Geology of the Nearby Sea Cliff Hydrothermal Vent Field From 1-M Resolution AUV Mapping

The northernmost segment of the Gorda mid-ocean ridge is the site of a small-volume eruption in 1996 and the persistent off-axis Sea Cliff hydrothermal vent field. To better understand the geologic setting and formation of these features, 1-m resolution bathymetric mapping using autonomous underwater vehicles was completed in 2016. The mapped region covers 35 km2 and 15.6 km of the volcanic axis from south of the 1996 lava flows, and a cross section for ∼4.5 km perpendicular to the axis, that extends beyond the Sea Cliff hydrothermal vent field. A proposed 1996 flow ∼7 km south of previously mapped flows is an artifact from a poor pre-eruption survey. The 1996 flows consist of three discrete steep hummocky mounds of pillows and syneruptive talus. The Sea Cliff hydrothermal field is located a few km north of the narrowest, shallowest section of the ridge segment, 2.6 km east of the center of the neovolcanic zone, and ∼370 m above the average depth of the axial graben on the largest offset ridge-parallel fault. No evidence supports the prior hypothesis that the site is located where two fault systems intersect. The axial graben is asymmetrical with larger fault offsets on the east side. The ridge axis below the hydrothermal field and to the south toward the 1996 flows is constructed dominantly of hummocky flows of pillow basalt, many unusually steep-sided, with syneruptive talus at the base of their steep slopes. Three channelized flows ponded between steep hummocky flows, and then partially drained. Some low-eruption-rate hummocky flows and high-eruption-rate channelized flows have nearly identical compositions, supporting the idea that eruption rates on mid-ocean ridges vary because of different dike widths. Four volcanic structures with volumes between 0.18 and 0.25 km3 occur in the axial graben south of the 1996 flows. Two are flat-topped cones, another is a 1.5-km diameter inflated hummocky flow with 7 pit craters that demonstrate that the flow had a molten interior during growth. The fourth voluminous structure is a steep ridge with abundant syneruptive talus on its lower slopes. The North Gorda segment is an end-member, structurally and volcanically, compared with other Pacific intermediate-rate spreading ridges