End Of Story Research Articles

Creatine for neuroprotection in neurodegenerative disease: end of story?

Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases.

Introduction

Questions of value might seem beyond the pale in cases of sound and music. Both are objects of immense accumulation, appreciation, exploration, and investment—not just for the human species but also among other species, and indeed the world. Sound simply is, its existence is inexhaustible, and remarkable things happen in and through it—end of story. Why, then, the question of value? Divesting sound and music from naive notions of intrinsic value, the essays here examine heterogeneous modalities by which sound and music produce value in and as history, politics, and ontology. In turn, the very question of what sound and music are—of what constitutes them, as well as what they constitute—is precisely what is at stake.

If you knew the end of a story would you still want to hear it? Using research poems to listen to Aboriginal stories

ABSTRACTThis paper presents a poem created whilst conducting an inquiry into one of the endings of stories told of, and by, people living with mental illness: this story ending is grouped by a word (and social movement) widely known as Recovery in mental health care. Recovery, however, is not a word commonly used in the places where this Inquiry occurred. Nor is it a category of story ending often told about Australian Aboriginal people living with a diagnosis of chronic mental illness. This inquiry was, and is, thus focussed on how the current endings of stories that surround Australian Aboriginal peoples in mental health care are being/were told and “heard”. This paper is an attempt to use poetry as a therapeutic and storytelling strategy to highlight the difference between hearing and listening, and how that difference relates to the word Recovery as a paradigm shift and story of social change.

“A Reading Problem”: Margaret Lynn, Jean Stafford, and Literary Criticism of the American West

“A Reading Problem”:Margaret Lynn, Jean Stafford, and Literary Criticism of the American West Cathryn Halverson I have borrowed the main title of this essay from one of Jean Stafford’s many autobiographical short stories, “A Reading Problem.” Recasting details of Stafford’s Boulder, Colorado girlhood, the story tracks the quest of its protagonist, Emily Vanderpool, to read in peace. Emily owns many books, including Tom Sawyer Abroad, Hans Brinker, and Rebecca of Sunnybrook Farm, but she has no place to read them free from the scrutiny of prying adults. A hotel lobby and the town jail prove to be only temporary solutions, and her dilemma leads to a fraught encounter with a con man and his daughter. The story ends with Emily’s revelation that the cemetery meets her needs. However, the rather portentous final image of her reading while seated “beside the grave of an infant kinswoman of the sheriff, a late-nineteenth-century baby called Primrose Starbird,” undermines any complacent resolution (344). Emily’s proximity to another bygone Colorado girl points at once toward familial connections between generations of western women and the inaccessibility of past stories. The evocative name on the stone is the only text the “infant kinswoman” offers her. This essay uncovers connections between western women writers by discussing Jean Stafford in concert with her literal kinswoman, Margaret Lynn. Author of the once widely known A Stepdaughter of the Prairie, Lynn was a native Missourian who preceded Stafford as an important spokeswoman of the West; she was also, not incidentally, Stafford’s first cousin once removed. The brunt of my argument is that Stafford and Lynn thematize, in their autobiographical texts, the difficulty of identifying a literary tradition shaped by western women. As critics, I posit, we experience this same difficulty—the same “reading problem” in respect to women writers and the West. Stafford’s three novels and many short stories established her as a leading [End Page 127] literary voice of the American West and “a figure of genuine consequence” in American letters more generally (Yardley). For over twenty years Stafford published short fiction in the New Yorker, a magazine with which she remains closely associated, and she won the 1970 Pulitzer Prize for Fiction for Collected Stories. Her oeuvre includes numerous expressions of the plight of the female intellectual coming of age in the American West—some comic, like “A Reading Problem,” and others tragic, like her best-known book, The Mountain Lion (1947). Stafford was deeply interested in the ramifications of being a western woman. She did not, however, openly explore relationships between women in the West. Women’s succor and bonds are present in her fiction only at a sedimentary level, as almost literally configured in the image of Emily Vanderpool reading beside Primrose Starbird’s grave. Stafford’s inclination to feature “woman” over “women”—to focus, that is, on individual female characters without making larger claims about women’s experience—is mirrored in dominant trends in western literary criticism. Key figures like Willa Cather, Mary Austin, Mourning Dove, and Laura Ingalls Wilder, to take some earlier twentieth-century examples, are typically treated in single-author studies. Correlatively, we have only a scant handful of monographs on “western women’s literature” as such. It is telling that Annette Kolodny’s The Land Before Her, published over three decades ago, remains the standard reference. In her review essay, “Big Books Wanted: Women and Western American Literature in the Twenty-First Century,” Victoria Lamont investigates the sources of this dearth. Her title references Christine Bold’s observation about the lack of major studies featuring “the explanatory patterns and causal narratives that would produce an alternative history of the literary West” (qtd. in Lamont 322). Lamont shows that the limited number of monographs is due partly to the long stretch of recovery work that had to come first, in a discipline that “emerged from the margins of a marginal field” (311). Yet the scarcity is now perpetuated by its achieved sophistication, with scholars favoring—over broad claims—the more focused arguments that case studies yield. “The increasing complexity of feminist work may have had the unintended consequence of allowing traditional master narratives to...

The influences of participation and moderation on the development of a sense of virtual community

Sense of virtual community SOVC is an important indicator of website satisfaction and leads to higher levels of trust online and website use. More than 1,000 online users were surveyed about their activities in web forums, particularly how they view and interact with comments at the end of news stories. Overall internet participation and gender are the key predictors of how important an individual will report SOVC is and how much SOVC individuals report experiencing. The study also suggests that the development and enforcement of norms on an online comment forum is important to SOVC. Moderation of web interactions is shown to have a significant impact on whether an individual finds virtual community important. Findings suggest that the management of online forums is important to the development of SOVC - individuals in the study who favoured forums that were less restricted also reported experiencing lower levels of virtual community.

Replica: Gemma; Lyra by Lauren Oliver

Reviewed by: Replica: Gemma; Lyra by Lauren Oliver April Spisak Oliver, Lauren Replica: Gemma; Lyra. Harper/HarperCollins, 2016 [544p] ISBN 978-0-06-239416-3 $19.99 Reviewed from galleys R Gr. 8-10 This dual book (flip the volume over to start the other story) offers two narratives showing intersecting events from different perspectives. Lyra’s half is gripping from the start, offering an insider description of the Haven Institute, a horrifying research facility where clones are treated like lab rats, injected with diseases, and [End Page 141] studied as long as they manage to survive, which generally isn’t long. Lyra has had enough short glimpses of kindness and the outside world that when the chance to escape comes up, she braves it with one other clone, or replica, heading out in search of something better. Gemma thinks she is a normal teen with strict parents, but it turns out her parents have shady connections with the Haven Institute, and Gemma may not be who she thinks she is. Gemma’s dysmorphic obsession with her weight is tedious, particularly when it continues even after she meets two kids who escaped from hellish conditions, but her slow evolution out of spoiled rich kid mode is authentic. Both stories end abruptly, leaving readers with intriguing open-ended questions about what awaits the teens; that’s especially true for Lyra, who learns a surprise about her identity. For writerly types, an author’s note does an effective job showing how books evolve from original sparks of ideas into something entirely different. Copyright © 2016 The Board of Trustees of the University of Illinois

A Sociological Approach to Institutional Communication: The Public Image in Organizational Administration in Education

<p class="apa">Acknowledging that the external context visibly affects any organization, this investigation seeks to constitute a specific contribution to the study of the importance of public image in organizational administration. To that end, a collection and documentary analysis of news stories from the newspaper <em>O Fayalense</em> on the <em>Asylum for the Disadvantaged Children of Horta</em> [<em>Asilo de Infância Desvalida da Horta</em>], an institution located on Faial Island, Azores, Portugal, covering the time period of 1858 to 1895, is performed. In the presentation and discussion of the results, a comparison is made between two periods that involve a single president because they vary in the type of news stories published (at the level of sources and subjects). It is concluded that the news stories published cover three large types of references, which, given the period in question, vary substantially: factual information (on the celebrations occurring in the asylum, communications about donations received and appreciation of benefactors, or institutional information on the elections of the asylum directorate), praise (regarding the asylum’s mission, operation, or administration), and censures (including responses to external criticism, criticism of previous managements, and stories regarding the asylum’s precarious circumstances). The implication of the study is that the importance of a positive public image, especially a positive image that is supportive of the leadership, should not be overlooked for the organizational administration to have greater chances of success.</p>

Books: How Do You Feel? An Interoceptive Moment with Your Neurobiological Self

AD (Bud) Craig Princeton University Press, 2014, HB, 368pp, £19.57, 978-0691156767 As a medical student in the 1970s I learned that there were two pathways from the body to the brain; one entered the spinal cord and ascended to the brain on the ipsilateral side, carrying discriminatory and pressure touch, and proprioception; the other immediately crossed and ascended on the contralateral side, carrying pain, temperature and something that was (very) vaguely described as ‘fine’ touch. Both these pathways ascended to the midbrain (thalamus) then projected to the somatosensory cortex. End of story. Enter Bud Craig, a mathematician who strayed into a neuroscience class where they …

A Family Sketch, and Other Private Writings

A Family Sketch, and Other Private Writings

The Emperor of Any Place by Tim Wynne-Jones (review)

Reviewed by: The Emperor of Any Place by Tim Wynne-Jones Karen Coats Wynne-Jones, Tim The Emperor of Any Place. Candlewick, 2015 [336p] ISBN 978-0-7636-6973-7 $17.99 Reviewed from galleys R* Gr. 7-10 Evan is stunned by the sudden death of his father. Not knowing what else to do, he calls his grandfather, Griff, a severe military man whom his father hated, to come help settle his dad’s affairs. Griff had little respect for his son, who fled to Canada to evade the draft during the Vietnam War, and it doesn’t initially look like things will go any better with his grandson. Meanwhile, a phone call alerts Evan to a family mystery involving Griff; prior to his death, his father had received a book containing a translation of the diary of a Japanese soldier from World War II who was isolated on an island in the Pacific. Evan becomes engrossed in the diary, which tells of an American soldier stranded on the island until Griff comes and rescues him. Questions remain: how does the story end for the Japanese soldier, and why does Griff want the diary to disappear? Evan and Griff walk a knife edge between contempt and suspicion in their dealings with each other, and their ultimate method of reaching détente is both moving and masterfully tied in with the diary itself. The layers of intergenerational strife, savage warfare, lingering suspicion and gradual healing are quilted into a warming narrative that is both uncompromisingly tragic and holistically redemptive. Readers will carry this haunting story with them for a long time. Copyright © 2015 The Board of Trustees of the University of Illinois

Minority educators discuss a public story that challenges social inclusion

Abstract This paper focuses on understanding professional development as an interactive social, cultural, and political process. Toward that end, we present an analysis of an innovative professional development activity with educators from a minority group in a social inclusion reform program who reflected on a news story of an event challenging the reform. Based on socio-cultural discourse theory, we posited that participants' interactions around the public story would reveal unique insights about implementations of the policy, and we posed questions about what those insights would be. Participants—174 Roma Pedagogical Assistants (PAs)—read, discussed, and wrote endings to the public story in a workshop during their professional training. Analyses of the public story discussions and original story endings by 24 groups of PAs emphasized the need for public authorities to enforce social inclusion policy in collaboration with a wide range of relevant stakeholders, including those in Roma communities. Participants reached this consensus through effortful argumentation about threats to integration indicated in the public story and their own deliberations about the need for justice for the entire community. This study offers evidence that policy subjects offer unique insights by interacting directly with one another around a relevant critical incident. We discuss implications of the study for research and practice of educational reform as an interactive process.

The Blind Boy & the Loon by A. Arnaquq-Baril

Arnaquq-Baril, Alethea. The Blind Boy & the Loon. Illus. Alethea Arnaquq-Baril and Dan Gies. Iqaluit, NU: Inhabit Media, Inc., 2014. Print.This volume is unique among Inhabit Media’s publications in that it is produced from an animated short film called Lumaajuuq by accomplished Inuit filmmaker Arnaquq-Baril. Both the text and the images have been converted from the film. Anarquq-Baril tells us that the story of Lumaajuuq is an old one and a very long one. She has adapted and shortened it for the film. It tells of a boy who was deliberately blinded by his mother and has his sight restored by a loon. Subsequently, he tricks his mother into spearing a whale that will pull her into the sea, where she drowns and turns into the narwhal. The story ends with the admonition that “every act of revenge is a link in a chain that can only be broken by forgiveness”.The text is brief and is presented in white on a black side-bar that runs to the left of each two-page image spread. The black side-bar adds to the overall visual darkness of the book, reflecting the darkness of the story. The images by Arnaquq-Baril and Daniel Gies are usually on black, dark blues, greys and browns. All of the images are uncluttered. The characters are drawn in profile, outlined in thick black line, while the backgrounds are shaded or layers of colour. In contrast to other parts of the images, the boy consistently has an unnaturally white face, which makes him the focal point of each image.Overall this book does successfully make the conversion from film to print and makes another traditional story accessible to new audiences. It would be a good addition to public school libraries, elementary school libraries and libraries collecting polar fiction.Highly recommended: 4 stars out of 4Reviewer: Sandy CampbellSandy is a Health Sciences Librarian at the University of Alberta, who has written hundreds of book reviews across many disciplines. Sandy thinks that sharing books with children is one of the greatest gifts anyone can give.

If You Knew the End of the Story, Would you Still Want to Hear It?: The Importance of Narrative Time for Mental Health Care

The origins of this paper lie in our experiences of having heard too many stories with the same outcome or ending in the field of inquiry and practice described as “Aboriginal Mental Health.” This paper was written in an attempt to make sense of these experiences. It does so by focussing on another type of outcome or story ending in mental health care/research contexts more widely known as [Recovery]. Not to be confused with the term recovery as it is used in addiction studies, the concept of [Recovery] currently underpinning mental health care policies and reform is at once a philosophy, a practice orientation, and a guiding value and principle. This paper emerged from a range of discussions about [Recovery] as a practice orientation and a particular type of story-ending told by those who receive and provide Aboriginal mental health care in North Queensland. Poetic inquiry was used as a way to respond to the questions that arose from these discussions. In the research projects and discussions that foreground and underpin this paper, the use of poetic reasoning and writing, evolved from using poetry as a reflective tool, to a being used as a method of data collection, data construction, analysis and interpretation (even though none of these words appropriately inscribe these aspects of research within Arts informed research practices). It is also posited as an aesthetic and ethical way of (re)presenting the results of inquiring. This paper (re)presents and unpacks a particular generated poem to demonstrate the approach (as it is and was) used. As an arts-informed approach to social inquiry and to writing, the purpose of this text is to open or introduce an awkward pause in an ongoing dialogue or conversation about Aboriginal people in mental health care and to amplify the Aboriginal voices informing the development of this text.

Change Agency for Systems Engineers

AbstractINCOSE aims to establish thought leadership and help the world tackle large problems and complex issues. Systems engineering can enable rational problem solving that considers multiple stakeholder needs and interconnections of many interacting parts. Yet many systems engineers have trouble influencing decisions within their own organization, leaving doubt as to the path from engineering technical systems to establishing thought leadership in the greater world.This paper describes the process of leading change, called “change agency,” as an evolution of a technical systems engineering career. Change agency makes use of skills learned in engineering, as extended to the social world. Learning change agency requires systems engineers to identify new skills, acquire new knowledge, and adapt to new philosophies, in order to prepare for, plan, and implement intelligent and lasting change.This paper begins with two stories of change that systems engineers have participated in, and asks whether standard, technical systems engineering would be enough to ensure the change is implemented. Then it shows the evolution required from standard systems engineering knowledge and skills to the knowledge and skills required to be a good Change Agent. Steps required to identify, plan, and implement a change are discussed. The story endings are shared with an explanation of the results. An appendix describes a self‐assessment tool to help the systems engineer identify which aspects of change agency should be the first to be developed further.

James MacMillan St Luke Passion, Barbican Centre, London

James MacMillan's new St Luke Passion is unusual. No longer does the Passion story end in the death of its principal character; there's a postlude that sees Christ resurrected. Neither is it peopled with singers acting out the traditional confrontations between Christ, Pilate and the High Priest; it starts instead with a brief setting of the Annunciation text found at the opening of St Luke's gospel. Unusual too is the small size of the orchestra – no trombones or tubas, one set of timpani as the sole percussion and an organ. Perhaps most surprising, however, is that the roles of Christus and Pilate, and indeed everyone else, are given to the choruses: a children's chorus for Christ, the other choirs acting as narrator.

For the Love of Horror

For the Love of Horror Jim McWilliams (bio) Nightmares Unhinged: Twenty Tales of Horror Joshua Viola, ed. Hex Publishers www.hexpublishers.com 280 Pages; Print, $12.99 In the interest of full disclosure, I’ll confess that I’m not a regular reader of horror fiction, so my impressions in this review are going to be those of a reader who has read widely in nineteenth-and twentieth-century literary fiction, but has only read a few of the classic authors of the genre: a lot of Poe, some Lovecraft, a smattering of Stephen King, a bit of Shirley Jackson. I consequently came to this new collection of contemporary horror, Nightmares Unhinged: Twenty Tales of Horror, with fresh eyes since I’d heard of only a few of its contributors, even though their biographical notes tout that nearly all are award winners in the genre, and I hadn’t read any of their works. Like most story collections, this one varies widely in the quality of its narratives: from somewhat trite and predictable to genuinely witty and original, from stylistically pedestrian to very well written. Six of the stories are written or co-written by the volume’s editor, Joshua Viola, including two under the pseudonym of “J. V. Kyle,” which is the pen name of Viola and Keith Ferrell. Although I found Viola’s own stories to be relatively good, his two collaborations with Ferrell are along his best, and the two stories by Ferrell writing solo, “Be Seated” and “Danniker’s Coffin,” are the very best in the collection. I suppose I liked the latter story better despite the fact that, as far as I can tell, “Danniker’s Coffin” isn’t really a “horror story.” Or, at least, it’s not as deep in the genre as some of the other stories (no blood and guts, no vampires, no things that go bump in the night). In short, it never lapses into cliché but, instead, tells the moving tale of an elderly man who finally resolves to change his failure of a life and assume the career for which he’d been destined by his family’s heritage: to be the maker of fine coffins. Although his forefathers had been skilled carpenters and built beautiful coffins, Lower Jim (so named since his father was Upper Jim) never quite mastered the tools to perfectly plane a piece of wood or get the corners of a coffin neatly joined. His grandfather and father encouraged him in woodworking, but when Lower Jim decided to give up, they allowed him to retire his apprentice tools and handle the family’s business accounts and act as the office manager. After his father’s death, however, the business ends and Lower Jim, who has never married, slowly descends into poverty. The story ends with a surprising, yet very logical, conclusion that allows Lower Jim a measure of dignity and grace as he, in shocking fashion, resolves to carry on his family’s legacy. Moreover, Ferrell’s writing, unlike the heavy-handedness so often prevalent in horror fiction, remains clear and true, with the occasional deft metaphor added to accentuate the story’s theme. An example is when Ferrell describes Lower Jim’s stoicism in the face of his disappointing life: “As with his father and grandfather, tears had been fenced off from him from the moment he lay swaddled on the ground beside the plot into which his mother was being lowered.” This image not only describes Lower Jim’s emotional state of being but it also reinforces his decision that he must build a high fence between his property and that of his neighbor’s to ensure his privacy. Moreover, the repeated passive voice emphasizes the extreme passivity that Lower Jim has exhibited for most of his life until he resolves, finally, to build a coffin. Unlike the realism of “Danniker’s Coffin,” Ferrell’s other story in this collection, “Be Seated,” is much more firmly rooted in the horror genre as it relates—through an unreliable first-person narrator—the tale of a mysterious conjurer and his armchair, which the narrator later inherits following the conjurer...

Virginity in Young Adult Literature after Twilight by Christine Seifert (review)

Reviewed by: Virginity in Young Adult Literature after Twilight by Christine Seifert Tharini Viswanath (bio) Virginity in Young Adult Literature after Twilight. By Christine Seifert. Lanham, MD: Rowman & Littlefield, 2015. According to Christine Seifert, “progressive” young adult romance novels have a lot in common with ideas that are thousands of years old. In this study, she analyzes some of the most popular young adult novels since 2005—based on reader favorites on Goodreads and Amazon—that present characters who want to have sex but cannot for the sake of preserving their virtue. Popular romance, Seifert argues, relies on the trope of “abstinence porn,” in which teens and, by extension, their virginities become objectified and readers are invited to participate in this eroticization of virginity (3). Chapter 1, “From Forever to Twilight,” briefly discusses the concept of the purity myth and its role in America’s cultural understanding of young girls. This notion of purity is reflected in adolescent literature, where “abstinence porn tells us that the most titillating aspect of a sexual relationship is obsessing about doing it [because] once you do it, it’s all over” (5). Invariably, Seifert claims, the characters are predominantly white teens in heteronormative relationships, and issues of race, gender, and sexuality are rarely (if at all) questioned (17–18). In chapter 2, Seifert deals with virginity and sex in paranormal novels after Twilight, with special emphasis on the couples in the Hush Hush series by Becca Fitzpatrick, the Mara Dyer series by [End Page 314] Michelle Hodkin, and the Wolves of Mercy Falls series by Maggie Stiefvater. Invariably, the heroines are “ordinary girls who are secretly extraordinary,” and only the “romantic hero” is able to see their extraordinariness from the very beginning (24). Chapter 3 focuses on the formulaic romances in dystopian fiction, where virginity is not a choice for female characters. In the three series Seifert examines—the Selection series by Kiera Cass, the Matched series by Ally Condie, and the Delirium series by Lauren Oliver—virginity is a requirement and is central to the plot: “marriage is the ultimate goal because it means the couple can finally have sex” (67). Similar issues are raised in chapter 4, which deals with contemporary teen romance, in which the protagonist’s virginity is once again equated with morality. All of the novels that Seifert examines are predictable to the last; she even provides her readers with charts that summarize the romantic relationship between characters based on their status as virgins, how dangerous they are to each other, the problem in their relationship, the sexual activities in which they partake, and how the story ends. While the romantic partners may or may not have sex in the text, the innocent female protagonists almost always marry their (dangerous and sometimes abusive) partners. According to Seifert, there are four recurring tropes associated with virginity. Most important, the female protagonist’s naïveté and lack of sexual awareness not only make her attractive, but are also instrumental in making a “bad boy” good. Second, women cannot be trusted with their own virginity and must rely on a paternalistic “virginity guardian” to step in and reinforce the rules. The idea of “true love as destiny” is critical to these romances, in which “teen relationships can and should last forever, even if the partners seem to be poor matches” (38). Finally, and most disturbingly, possessive behavior and potentially dangerous people are portrayed as sexy and tempting, and violence is central to most of the novels that Seifert examines. Particularly insightful is her observation that virgins retain their virginal status even after they have had sex, as the “protagonist will remain pure for [her] one special and fated partner” (38). Arguably, the seemingly repetitive text serves to highlight the fact that the same ideology (sex is bad, abstinence is good) recurs in each of these novels, albeit with slightly varied plot lines. In a nutshell, virginity is less about sexual intercourse than it is about good behavior and moral quality; female nonvirgins become the young adult romance novel’s designated antagonists and are depicted as lacking in moral values because they acknowledge their sexuality. Chapters 5 and 6 help place Seifert’s...

No-Reflow Fenomeni: Hikayenin Sonu mu?

No-Reflow Fenomeni: Hikayenin Sonu mu?

Successes and Challenges on the Road to Cure Hepatitis C.

Hepatitis C virus (HCV) represents a significant health burden worldwide, with an estimated 185 million people chronically infected [1]. A leading cause of liver transplantation, HCV infection can result in severe liver disease including cirrhosis and hepatocellular carcinoma [2]. Cure of HCV infection results in substantial decreases in such liver-related morbidity and mortality [3]. Prior therapies for HCV offered only 40% cure for the most difficult-to-treat genotype-1 infection, required 48 weeks of therapy with an injectable interferon, and included significant adverse events [4]. The past year has seen the approval of five interferon-free direct-acting antiviral (DAA) regimens for HCV, including combinations of DAAs and fixed-dose combination pills (Tables ​(Tables11 and ​and2)2) [5–13]. Sustained virologic response (SVR), the virologic surrogate for clinical cure, has improved to >90% for most populations across all HCV genotypes (Table 2). While the successes attributable to DAA combination therapies will be many, there also remain challenges and much for us to learn as we embark on this journey to eradicate HCV. Here, we will discuss several of the greatest successes and future challenges in HCV therapeutics today. Table 1 All-oral direct acting antiviral regimens available for clinical use. Table 2 Sustained virologic response for all-oral direct acting antiviral regimens. Potent DAA Combinations Are Closing the Gap for Unique Patient Populations Although all patients with HCV infection will benefit from the availability of oral DAA combination therapies, several unique patient populations have seen dramatic improvements in SVR, revealing the great clinical impact of these therapies. Specifically, patients with HIV/HCV dual infection, patients with compensated and decompensated cirrhosis, and patients who have had liver transplantation for HCV-associated liver disease are exhibiting fantastic (87%–98%) SVR rates with oral DAA combination therapy [14–16]. These patients, who have a greater risk of progression of liver disease, hepatocellular carcinoma, and death, previously had low response rates or even absolute contraindications to treatments with interferon [17–18]. The potential impact of HCV eradication for these highest-risk populations could be enormous, including decreases in hepatocellular carcinoma and liver transplantation, as well as prolonged survival for those already living with liver grafts. And yet, we do not know for sure how this story ends. While the liver has the ability to repair injured tissue [19] and there is evidence to suggest that fibrosis induced by chronic HCV infection is reversible [3], is there a point of no return? Previously, patients with HCV-associated decompensated liver disease (ascites, hepatic encephalopathy, and variceal bleeding) had only one choice for survival: organ transplantation. Is viral eradication enough to change their fate? The largest study to date in patients with decompensated cirrhosis reported SVR of nearly 90% with a DAA combination regimen [15]. Importantly, the study also reported on improvement in serum markers of synthetic liver function for a majority (>50%) of patients at post-treatment week 4. Whether these improvements translate to improved clinical outcomes over time remains to be seen, but there is reason for optimism.

Children's understanding of embarrassment: Integrating mental time travel and mental state information

The current study investigated 4- to 8-year-olds' (N=81) understanding of embarrassment and their ability to integrate temporal and mental state information to predict and explain emotions. Participants heard stories describing characters commit trivial social transgressions, and then the next day, characters found themselves in the same situation that led to the previous transgression. For some story endings, participants were asked to predict and explain how the character felt, and for others, participants were told the character started to feel embarrassed and they were asked to explain why. Participants' responses were coded and analysed using nonparametric statistical tests. Kruskal-Wallis analyses revealed significant developments occur between 6 and 8years in children's understanding of embarrassment and their ability to explain individual's emotion as caused by anticipating the reoccurrence of a previous embarrassing event. Younger children demonstrated a basic knowledge of embarrassment but failed to demonstrate more advanced understanding of the emotion. Findings from the current study indicate children reach a more mature understanding of embarrassment and the implications of committing social transgressions between 7 and 8years. Finally, the current study contributes to the literature on children's ability to infer mental states and temporally connect experiences.