Clinical manifestations in patients with PI*MMMalton genotypes. A matter still unsolved in alpha-1 antitrypsin deficiency

We report the genetic variants associated with alpha-1 antitrypsin deficiency (AATD) in 117 patients admitted to our outpatient clinic and characterized by a serum concentration of AAT lower than 113 mg/dL. We focused on the M-like heterozygous variant of the SERPINA1 gene called PI*MMMalton, and describe three patients with this variant. While the role of homozygous AATD in liver and pulmonary disease is well established, the association between heterozygous AATD and chronic liver and pulmonary disease is still under investigation. The PI*MMMalton genotype was found in 5.8% of patients with a pathological genotype of AATD and in 14.3% of the subjects when considering only those with intermediate AATD. There were no liver or renal abnormalities in patients with the PI*MMMalton genotype. The PI*MMMalton patients included here showed a normal liver function, and none had renal function abnormalities or abdominal aortic aneurysm. Only a prevalence of lung disease was detected

Concurrent Computing with Shared Replicated Memory

The behavioural theory of concurrent systems states that any concurrent system can be captured by a behaviourally equivalent concurrent Abstract State Machine (cASM). While the theory in general assumes shared locations, it remains valid, if different agents can only interact via messages, i.e. sharing is restricted to mailboxes. There may even be a strict separation between memory managing agents and other agents that can only access the shared memory by sending query and update requests to the memory agents. This article is dedicated to an investigation of replicated data that is maintained by a memory management subsystem, whereas the replication neither appears in the requests nor in the corresponding answers. We show how the behaviour of a concurrent system with such a memory management can be specified using concurrent communicating ASMs. We provide several refinements of a high-level ground model addressing different replication policies and internal messaging between data centres. For all these refinements we analyse their effects on the runs such that decisions concerning the degree of consistency can be consciously made.Comment: 23 page

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database

Lung structure and function; COPD and smokingEstructura y función pulmonar; EPOC y tabaquismoEstructura i funció pulmonar; MPOC i tabaquismeBackground Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). Methods To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Results Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71). Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.This study was supported by Stichting AIR

α1-Antitrypsin deficiency.

α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development

The dust envelope of the pre-planetary nebula IRAS19475+3119

We present the spectral energy distribution (SED) of the pre-planetary nebula, IRAS 19475+3119 (I19475), from the optical to the far-infrared. We identify emission features due to crystalline silicates in the ISO SWS spectra of the star. We have fitted the SED of I19475 using a 1-D radiative transfer code, and find that a shell with inner and outer radii of 8.8X10^{16} and 4.4X10^{17}cm, and dust temperatures ranging from about 94K to 46K provide the best fit. The mass of this shell is greater than/equal to 1[34cm^{2}g^{-1}/kappa(100micron)][delta/200]M_Sun, where kappa(100micron) is the 100micron dust mass absorption coefficient (per unit dust mass), and delta is the gas-to-dust ratio. In agreement with results from optical imaging and millimeter-wave observations of CO emission of I19475, our model fits support an r^{-3} density law for its dust shell, with important implications for the interaction process between the fast collimated post-AGB winds and the dense AGB envelopes which results in the observed shapes of PPNs and PNs. We find that the observed JCMT flux at sub-millimeter wavelengths (850micron) is a factor ~ 2 larger than our model flux, suggesting the presence of large dust grains in the dust shell of I19475 which are not accounted for by our adopted standard MRN grain size distribution.Comment: 38 pages, 8 figures. Accepted for publication in Ap

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients : an analysis of the AIR database

Background Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). Methods To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Results Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±SD follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups ( p=0.71). Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy

When an old star smolders: On the detection of hydrocarbon emission from S-type AGB stars

Polycyclic aromatic hydrocarbons (PAHs) produce characteristic infrared emission bands that have been observed in a wide range of astrophysical environments, where carbonaceous material is subjected to ultraviolet (UV) radiation. Although PAHs are expected to form in carbon-rich AGB stars, they have up to now only been observed in binary systems where a hot companion provides a hard radiation field. In this letter, we present low-resolution infrared spectra of four S-type AGB stars, selected from a sample of 90 S-type AGB stars observed with the infrared spectrograph aboard the Spitzer satellite. The spectra of these four stars show the typical infrared features of PAH molecules. We confirm the correlation between the temperature of the central star and the centroid wavelength of the 7.9 {\mu}m feature, present in a wide variety of stars spanning a temperature range from 3 000 to 12 000 K. Three of four sources presented in this paper extend this relation towards lower temperatures. We argue that the mixture of hydrocarbons we see in these S-stars has a rich aliphatic component. The fourth star, BZ CMa, deviates from this correlation. Based on the similarity with the evolved binary TU Tau, we predict that BZ CMa has a hot companion as well.Comment: 5 pages, 2 figures, 2 table

Dust Emission Features in NGC 7023 between 0.35 and 2.5 micron: Extended Red Emission (0.7 micron) and Two New Emission Features (1.15 and 1.5 micron)

We present 0.35 to 2.5 micron spectra of the south and northwest filaments in the reflection nebula NGC 7023. These spectra were used to test the theory of Seahra & Duley that carbon nanoparticles are responsible for Extended Red Emission (ERE). Our spectra fail to show their predicted second emission band at 1.0 micron even though both filaments exhibit strong emission in the familiar 0.7 micron ERE band. The northwest filament spectrum does show one, and possibly two, new dust emission features in the near-infrared. We clearly detect a strong emission band at 1.5 micron which we tentatively attribute to beta-FeSi_2 grains. We tentatively detect a weaker emission band at 1.15 micron which coincides with the location expected for transitions from the conduction band to mid-gap defect states of silicon nanoparticles. This is added evidence that silicon nanoparticles are responsible for ERE as they already can explain the observed behavior of the main visible ERE band.Comment: 9 pages, color figures, accepted to the ApJ, color and b/w versions available at http://dirty.as.arizona.edu/~kgordon/papers/ere_1um.htm