Development of a Consensus Statement for the Definition, Diagnosis, and Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis Using the Delphi Technique.

© 2015, The Author(s).Introduction: There is a lack of agreed and established guidelines for the treatment of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This reflects, in part, the limited evidence-base underpinning the management of AE-IPF. In the absence of high-quality evidence, the aim of this research was to develop a clinician-led consensus statement for the definition, diagnosis and treatment of AE-IPF. Methods: A literature review was conducted to obtain published material on the definition and treatment of AE-IPF. The results of this review were circulated to an online panel of clinicians for review. Statements were then shared with ten expert respiratory clinicians who regularly treat patients with IPF. A Delphi technique was then used to develop a consensus statement for the definition, diagnosis and treatment of AE-IPF. During the first round of review, clinicians rated the clarity of each statement, the extent to which the statement should be included and provided comments. In two subsequent rounds of review, clinicians were provided with the group median inclusion rating for each statement, and any revised wording of statements to aid clarity. Clinicians were asked to repeat the clarity and inclusion ratings for the revised statements. Results: The literature review, online panel discussion, and face-to-face meeting generated 65 statements covering the definition, diagnosis, and management of AE-IPF. Following three rounds of blind review, 90% of clinicians agreed 39 final statements. These final statements included a definition of AE-IPF, approach to diagnosis, and treatment options, specifically: supportive measures, use of anti-microbials, immunosuppressants, anti-coagulants, anti-fibrotic therapy, escalation, transplant management, and long-term management including discharge planning. Conclusion: This clinician-led consensus statement establishes the ‘best practice’ for the management and treatment of AE-IPF based on current knowledge, evidence, and available treatments. Funding: Boehringer Ingelheim Ltd., Bracknell, West Berkshire, UK

On the goursat problem for a linear partial differential equation

In this paper, the Goursat problem of a general form for a linear partial differential equation is investigated with the help of the Riemann function method. Some results are given concerning the existence and uniqueness for the solution of the suggested problem

On a characteristic problem for a third order pseudoparabolic equation

In this paper, we investigate the Goursat problem in the class C2+1(D)∩Cn+0(D∪P) ∩C0+0(D∪Q) for a third order pseudoparabolic equation. Some results are given concerning the existence and uniqueness for the solution of the suggested problem. © Shiraz University

The variant of the Goursat problem for the sixth order equation

Our study is considered as a continuation of results in [1-8]. More precisely we investigate the Goursat problem in class C2+2+2(D) for the equation (1) below by Riemann method variant from the works [8] and [9]

Progesterone utility in the synthesis of steroidal heterocyclic compounds with antitumor activity

One–pot and efficient method for the synthesis of progesteronpyridine 5a-c, 6a-c and 7a,b and/or progesteronpyran derivatives 9a-c and 10a,b by condensation reaction of progesterone 1 with different aldehydes and active methylene compounds in the presence of ammonium acetate or piperidine.  New progesteronopyrimidine derivatives 12a-d and 13a, b were synthesized via interaction of progesterone 1 with urea or thiourea and/or guanidine reagents and aldehyde. Progesterone 1 was examined to synthesize heterocyclic compound 16 containing ?-Lactone chiral carbon via the reaction of hydrazone derivative 14 with phenyl isothiocyanate followed by boiling with chloroacetic acid in benzene. The biological activity of compounds 5a, 5b, 6b, 7a, 9b, 9c, 12a, 12c, and 13a were evaluated as growth inhibitors of the liver and the breast carcinoma human cell line (HEPG2 & MCF7). Compounds 13a, 12a and 7a showed a higher potency than the standard. Key Words: Progesterone, MCR’s (multicomponents reaction), (pyridine, pyran, pyrimidine, ?-Lactone) derivatives, HEPG2 & MCF7

Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of prostate cancer. Although long-noncoding RNAs (lncRNAs) have been implicated in mCRPC, past studies have relied on bulk sequencing methods with low depth and lack of single-cell resolution. Hence, we performed a lncRNA-focused analysis of single-cell RNA-sequencing data (n = 14) from mCRPC biopsies followed by integration with bulk multi-omic datasets. This yielded 389 cell-enriched lncRNAs in prostate cancer cells and the tumor microenvironment (TME). These lncRNAs demonstrated enrichment with regulatory elements and exhibited alterations during prostate cancer progression. Prostate-lncRNAs were correlated with AR mutational status and response to treatment with enzalutamide, while TME-lncRNAs were associated with RB1 deletions and poor prognosis. Finally, lncRNAs identified between prostate adenocarcinomas and neuroendocrine tumors exhibited distinct expression and methylation profiles. Our findings demonstrate the ability of single-cell analysis to refine our understanding of lncRNAs in mCRPC and serve as a resource for future mechanistic studies

Submarine landslides in the Santa Barbara Channel as potential tsunami sources

International audienceRecent investigations using the Monterey Bay Aquarium Research Institutes (MBARI) Remotely Operated Vehicles (ROVs) "Ventana" and "Tiburon" and interpretation of MBARI's EM 300 30 kHz multibeam bathymetric data show that the northern flank of the Santa Barbara Basin has experienced massive slope failures. Of particular concern is the large (130 km2) Goleta landslide complex located off Coal Oil Point near the town of Goleta, that measures 14.6-km long extending from a depth of 90 m to nearly 574 m deep and is 10.5 km wide. We estimate that approximately 1.75 km3 has been displaced by this slide during the Holocene. This feature is a complex compound submarine landslide that contains both surfical slump blocks and mud flows in three distinct segments. Each segment is composed of a distinct head scarp, down-dropped head block and a slide debris lobe. The debris lobes exhibit hummocky topography in the central areas that appear to result from compression during down slope movement. The toes of the western and eastern lobes are well defined in the multibeam image, whereas the toe of the central lobe is less distinct. Continuous seismic reflection profiles show that many buried slide debris lobes exist and comparison of the deformed reflectors with ODP Drill Site 149, Hole 893 suggest that at least 200 000 years of failure have occurred in the area (Fisher et al., 2005a). Based on our interpretation of the multibeam bathymetry and seismic reflection profiles we modeled the potential tsunami that may have been produced from one of the three surfical lobes of the Goleta slide. This model shows that a 10 m high wave could have run ashore along the cliffs of the Goleta shoreline. Several other smaller (2 km2 and 4 km2) slides are located on the northern flank of the Santa Barbara Basin, both to the west and east of Goleta slide and on the Conception fan along the western flank of the basin. One slide, named the Gaviota slide, is 3.8 km2, 2.6 km long and 1.7 km wide. A distinct narrow scar extends from near the eastern head wall of this slide for over 2km eastward toward the Goleta slide and may represent either an incipient failure or a remnant of a previous failure. Push cores collected within the main head scar of this slide consisted of hydrogen sulfide bearing mud, possibly suggesting active fluid seepage and a vibra-core penetrated ~50 cm of recent sediment overlying colluvium or landslide debris confirming the age of ~300 years as proposed by Lee et al. (2004). However, no seeps or indications of recent movement were observed during our ROV investigation within this narrow head scar indicating that seafloor in the scar is draped with mud