Diagnosing fibrotic lung disease: When is high-resolution computed tomography sufficient to make a diagnosis of idiopathic pulmonary fibrosis?

Idiopathic pulmonary fibrosis (IPF), a progressive and fatal diffuse parenchymal lung disease, is defined pathologically by the pattern of usual interstitial pneumonia (UIP). Unfortunately, a surgical lung biopsy cannot be performed in all patients due to comorbidities that may significantly increase the morbidity and mortality of the procedure. High-resolution computed tomography (HRCT) has been put forth as a surrogate to recognize pathological UIP. The quality of the HRCT impacts the ability to make a diagnosis of UIP and varies based on the centre performing the study and patient factors. The evaluation of the HRCT includes assessing the distribution and predominance of key radiographical findings, such as honeycomb, septal thickening, traction bronchiectasis and ground glass attenuation lesions. The combination of the pattern and distribution is what leads to a diagnosis and associated confidence level. HRCT features of definite UIP (subpleural, basal predominant honeycomb with septal thickening, traction bronchiectasis and ground glass attenuation lesions) have a high specificity for the UIP pathological pattern. In such cases, surgical lung biopsy can be avoided. There are caveats to using the HRCT to diagnose IPF in isolation as a variety of chronic pulmonary interstitial diseases may progress to a UIP pattern. Referral centres with experience in diffuse parenchymal lung disease that have multidisciplinary teams encompassing clinicians, radiologists and pathologists have the highest level of agreement in diagnosing IPF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75246/1/j.1440-1843.2009.01626.x.pd

Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150609/1/art40862.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150609/2/art40862_am.pd

Comparison of disease progression and mortality of connective tissue disease-related interstitial lung disease and idiopathic interstitial pneumonia

Objective To compare disease progression and mortality between idiopathic interstitial pneumonia (IIP) and interstitial lung disease (ILD) due to connective tissue diseases (CTD) including scleroderma, rheumatoid arthritis, systemic lupus, polymyositis, dermatomyositis, SjÖgren's syndrome, and mixed CTD. Methods A case-control study of patients with CTD-ILD (n = 46) and IIP controls (n = 51), seen at the University of Michigan between July 1,1998 and June 30,1999 and followed until March 30, 2002, was conducted. Survival analysis and Cox regression were performed to estimate survival, accounting for demographic and clinical parameters, including pulmonary function tests and high resolution computed tomography (HRCT) diagnosis and scoring. Results Median followup time was 4.4 person-years. Five-year survival in the IIP group was 51.9% (95% confidence interval [95% CI] 30.8–69.4) versus 43.4% (95% CI 21.1–63.9) in the CTD-ILD group. There were no significant differences among HRCT diagnostic categories between IIP and CTD-ILD. A fibrotic score ≥2 was associated with decreased survival among the entire group. Age at diagnosis and most recent forced vital capacity were significant predictors of mortality when adjusted for IIP versus CTD-ILD diagnosis, sex, and interstitial score. Conclusion Contrary to expectation, CTD-ILD compared with IIP appears to be associated with a worse prognosis when adjusted for age. A higher fibrotic score is suggestive of decreased survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48677/1/21322_ftp.pd

Spitzer Imaging of the Nearby Rich Young Cluster, Cep OB3b

We map the full extent of a rich massive young cluster in the Cep OB3b association with the IRAC and MIPS instruments aboard the {\it Spitzer} Space Telescope and the ACIS instrument aboard the $\it{Chandra}$ X-Ray Observatory. At 700 pc, it is revealed to be the second nearest large ($>1000$ member), young ($< 5$ Myr) cluster known. In contrast to the nearest large cluster, the Orion Nebula Cluster, Cep OB3b is only lightly obscured and is mostly located in a large cavity carved out of the surrounding molecular cloud. Our infrared and X-ray datasets, as well as visible photometry from the literature, are used to take a census of the young stars in Cep OB3b. We find that the young stars within the cluster are concentrated in two sub-clusters; an eastern sub-cluster, near the Cep B molecular clump, and a western sub-cluster, near the Cep F molecular clump. Using our census of young stars, we examine the fraction of young stars with infrared excesses indicative of circumstellar disks. We create a map of the disk fraction throughout the cluster and find that it is spatially variable. Due to these spatial variations, the two sub-clusters exhibit substantially different average disk fractions from each other: $32$ and $50$. We discuss whether the discrepant disk fractions are due to the photodestruction of disks by the high mass members of the cluster or whether they result from differences in the ages of the sub-clusters. We conclude that the discrepant disk fractions are most likely due to differences in the ages.Comment: 48 Pages, 12 figures, 6 table

NASA IceCube: CubeSat Demonstration of a Commercial 883-GHz Cloud Radiometer

On April 18 2017, NASA Goddard Space Flight Center's IceCube 3U CubeSat was launched by an ATLAS V rocket from Cape Canaveral Air Force Station on board a Cygnus resupply spacecraft, as part of NASA's CubeSat Launch Initiative. Onboard IceCube was an 883 GHz radiometer tuned to detecting ice content in clouds, marking the first time such frequency was used from low-Earth orbit. IceCube successfully demonstrated retrieval of ice water path, generating the first ever global cloud ice map at 883 GHz. Its success provides valuable lessons on how to approach a severely resource-limited space mission and provides great insight into how this experience can be applied to future high-risk, "non-class" missions for NASA and others. IceCube marks the first official NASA Earth Science CubeSat technology demonstration mission. The spacecraft was completed in about 2.5 years starting April 2014 through launch provider delivery in December of 2016. The mission was jointly funded by NASA's Earth Science Technology Office, after competitive selection, and by NASA's Earth Science Directorate. IceCube began its technology demonstration mission in June 2017, providing a pathway to advancing the understanding of ice clouds and their role in climate models; quite a tall order for a tiny spacecraft

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

MBM 12: young protoplanetary discs at high galactic latitude

(abridged) We present Spitzer infrared observations to constrain disc and dust evolution in young T Tauri stars in MBM 12, a star-forming cloud at high latitude with an age of 2 Myr and a distance of 275 pc. The region contains 12 T Tauri systems, with primary spectral types between K3 and M6; 5 are weak-line and the rest classical T Tauri stars. We first use MIPS and literature photometry to compile spectral energy distributions for each of the 12 members in MBM 12, and derive their IR excesses. The IRS spectra are analysed with the newly developed two-layer temperature distribution (TLTD) spectral decomposition method. For the 7 T Tauri stars with a detected IR excess, we analyse their solid-state features to derive dust properties such as mass-averaged grain size, composition and crystallinity. We find a spatial gradient in the forsterite to enstatite range, with more enstatite present in the warmer regions. The fact that we see a radial dependence of the dust properties indicates that radial mixing is not very efficient in the discs of these young T Tauri stars. The SED analysis shows that the discs in MBM 12, in general, undergo rapid inner disc clearing, while the binary sources have faster discevolution. The dust grains seem to evolve independently from the stellar properties, but are mildly related to disc properties such as flaring and accretion rates.Comment: 14 pages, accepted by Astronomy and Astrophysic

Long-Term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety

INTRODUCTION: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years. METHODS: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, and serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses. RESULTS: Of 1,298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA &lt;29 IU/mL (missing 5 failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median estimated glomerular filtration rate (by using Cockcroft-Gault) declined &lt;2.5 mL/min, and mean declines of &lt;1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF. DISCUSSION: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.</p