Diminishing Use of Liver Biopsy among Liver Transplant Recipients for Hepatitis C.

Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation

Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.

Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects

A New Generation of Peptide-based Inhibitors Targeting HIV-1 Reverse Transcriptase Conformational Flexibility.

International audienceThe biologically active form of human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is a heterodimer. The formation of RT is a two-step mechanism, including a rapid protein-protein interaction "the dimerization step," followed by conformational changes "the maturation step," yielding the biologically active form of the enzyme. We have previously proposed that the heterodimeric organization of RT constitutes an interesting target for the design of new inhibitors. Here, we propose a new class of RT inhibitors that targets protein-protein interactions and conformational changes involved in the maturation of heterodimeric reverse transcriptase. Based on a screen of peptides derived from the thumb domain of this enzyme, we have identified a short peptide P(AW) that inhibits the maturation step and blocks viral replication at subnanomolar concentrations. P(AW) only binds dimeric RT and stabilizes it in an inactive/non-processive conformation. From a mechanistic point of view, P(AW) prevents proper binding of primer/template by affecting the structural dynamics of the thumb/fingers of p66 subunit. Taken together, these results demonstrate that HIV-1 RT maturation constitutes an attractive target for AIDS chemotherapeutics

The development of therapy suggestions for addressing issues of creativity in individuals diagnosed with bipolar disorder

The aim of the present study was to generate a set of therapy suggestions specifically for use in the treatment of creative individuals diagnosed with bipolar disorder. In order to achieve this end, the author collected information from bodies of literature that focused on three general research areas: (a) the relationship between bipolar illness and creativity, (b) the treatment of bipolar individuals, and (c) psychotherapy treatment of creative individuals. The information gleaned from these three areas was synthesized and used to inform the general treatment suggestions. This study examined several of the existing approaches to the treatment of bipolar disorder and provided suggestions for ways in which those treatments could be tailored for use with creative clients who are diagnosed with bipolar disorder. Effective psychiatric and psychological (i.e., psychotherapeutic) interventions have been developed for the treatment of individuals diagnosed with bipolar disorder, though additional research can be conducted to better understand how these interventions can be adapted to improve outcomes with certain clinical subgroups. Creative individuals with bipolar disorder reflect one such subgroup, and it is hoped that the suggestions for therapeutic adaptations contained within this dissertation begin to draw more attention to an under-researched group

Product Designs that Enchant, Transform, and Endure

For many reasons – sustainability, product aesthetics, market demand for authenticity – there appears to be growing interest in classic products, products that are owned for a long time and stay on the market a long time. This is a conceptual paper which investigates these questions: What is classic art? What are classic product designs? What learning can be applied from classic art and classic product designs to new product designs? Art historians argue that classic art endures because its meanings constantly evolve. This paper reviews the semantic evolution of a classic novel, and the evolution of a classic product, the Austin Mini car. The design evolution of the Mini as well as many other classic products suggests a different design approach than recent approaches which focus on individual target segments, core product meanings, and brand identities. Classic design approaches suggest multiple targets, design ambiguity, and a brand focus on designer identity

Transonic conical flow

The problem of inviscid, steady transonic conical flow, formulated in terms of the small disturbance theory, is studied. The small disturbance equation and similarity rules are presented, and a boundary value problem is formulated for the case of a supersonic freestream Mach number. The equation for the perturbation potential is solved numerically using an elliptic finite difference system. The difference equations are solved with a point relaxation algorithm that is also capable of capturing the shock wave during the iteration procedure by using the boundary conditions at the shock. Numerical calculations, for shock location, pressure distribution and drag coefficient, are presented for a family of nonlifting conical wings. The theory of slender wings is also presented and analytical results for pressure and drag coefficients are obtained

Moving toward personalizing MELD exceptions in liver transplantation for hepatocellular carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150509/1/ajt15389_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150509/2/ajt15389.pd

Urban Modernization of Late Ottoman Kadıköy and the Memoirs of Hovhannes Kalfa Stepanian

This article explores the urban modernization of late Ottoman Kadıköy through the lens of Hovhannes Kalfa Stepanian’s memoirs. A local inhabitant of Kadıköy and an active stonemason that oversaw the construction of several buildings in his district, Stepanian was an avid observer and passionate archivist of the eventful decades that shaped the urban fabric of modern Kadıköy. His memoirs contain precious visual and textual material including hand-drawn maps and neighborhood plans, property transactions, and patterns of the transformation of agricultural fields into real estate commodities. This article puts Stepanian’s hitherto untapped memoirs into historical perspective and offers a narrative of late Ottoman urban modernization that centers on the inhabitants of a semt (quarter) and the dynamics of the real estate market rather than the imperial and communal perspectives and practices. © 2024 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement

Vzdělávání učitelů v Libanonu: Srovnání programů na univerzitách amerického a francouzského modelu

Vysokoškolské vzdělávání v Libanonu je rozmanité a univerzity se dělí podle uplatněného modelu vzdělávání, jako například americký či francouzský. Tato disertační práce se držela vnitronárodního srovnávacího přístupu, aby porovnala programy vzdělávání učitelů na vysokých školách amerického a francouzského modelu v Libanonu. Bylo vybráno šest univerzit, tři z každého modelu. Cílem bylo popsat strukturu a obsah programů, prozkoumat vnímanou efektivitu programů na základě informací od absolventů a porovnat programy v indikátorech praktických zkušeností, reflektivní praxe a získávání základů znalostí. Srovnání bylo provedeno s využitím zavedených teorií jako měřítek: Feiman-Nemserova typologie koncepčních orientací v programech vzdělávání učitelů, teorie Lee Shulmana o získávání znalostních základů budoucími učiteli a teorie Freda Korthagena o začlenění reflektivní praxe do vzdělávání učitelů. K prozkoumání struktury a obsahu programů byla použita metoda analýzy dokumentů a byly provedeny polostrukturované rozhovory s dvaceti absolventy šesti vybraných univerzit amerického a francouzského vzoru s cílem zjistit vnímanou efektivitu programů při přípravě studentů na učitelství. Výsledky ukázaly podobnosti a rozdíly mezi univerzitami amerického a francouzského modelu, například potřebu zvýšení přípravy...Oddělení pro vědeckou činnostFaculty of EducationPedagogická fakult