138 research outputs found
Comparative efficacy and acceptability of pharmacological treatments for insomnia in adults: a systematic review and network meta-analysis
No full textThis is the protocol for a review and there is no abstract. The objectives are as follows: 1) To compare individual pharmacological treatments for insomnia in adults in terms of: efficacy, measured as self-rated quality of sleep or satisfaction with sleep; and acceptability of treatment. 2) To generate a clinically-useful hierarchy of available pharmacological treatments for insomnia in adults, according to their efficacy and acceptability
Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
No full textBACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre
Serotonin receptor mechanisms in anti-depressant action
No full textBibliography: leaves 221-270.Serotonin neurones have been implicated in the pathophysiology and treatment of clinical depression to a greater degree than any other neurotransmitter. Additionally, serotonin pathways may playa role in the pathophysiology and treatment of eating disorders, anxiety states and schizophrenia. Molecular biological studies have confirmed pharmacological evidence suggesting the existence of multiple serotonin receptor subtypes and the genes for these receptors, as well as that of the serotonin transporter, have common polymorphic variants. To investigate the effect of repeated treatment with selective serotonin fe-uptake inhibitors (SSRI's) on the function of central 5-HT2C receptors. To assess the effect of polymorphic variation in the 5-HT2c receptor and serotonin transporter on functional responses to selective pharmacological challenge. To determine whether polymorphic variation in the 5-HT receptor and serotonin transporter influence the clinical response of patients with major depression to treatment with serotonergic antidepressants. To assess the effect of repeated treatment with selective serotonin re-uptake inhibitors (SSRI's) on the function of central 5-HT2c receptors I used the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP) as a 5-HT2c probe in a neuroendocrine challenge paradigm. I used the same approach to assess whether polymorphic variation in the 5-HT2c receptor (serine vs cysteine substitution) was associated with differences in functional response to 5-HT2C receptor challenge. I then studied whether polymorphic variation in the serotonin transporter promotor region (long versus short form) was associated with differing functional responses to acute challenge with clomipramine, a tricyclic antidepressant with a high affinity for the serotonin transporter. Finally, I studied whether either of these polymorphic variants influenced the clinical response of patients with major depression to treatment with SSRI's and clomipramine. SSRI treatment significantly lowered the sensitivity of 5-HT2c receptors as predicted from animal experimental studies. However polymorphic variation in the 5-HTzc receptor did not significantly influence functional responses to m-CPP challenge. In contrast polymorphic variation in the serotonin transporter was associated with differing neuroendocrine responses to acute clomipramine challenge with greater prolactin release being seen in subjects with the long polymorphic variant. Neither the 5-HTzc nor the transporter polymorphisms correlated with clinical response to SSRI and clomipramine treatment in patients with major depression. The ability of SSRI's to produce a functional down-regulation of 5-HTzc receptors may be relevant to certain of their therapeutic effects. Polymorphic variation in the 5-HT2c receptor (serine vs cysteine) seems unlikely to explain functional differences in responses to 5-HTzc receptor challenge or antidepressant responses to SSRI treatment. In contrast variation in the serotonin transporter promotor is associated with differing functional responses to acute serotonin re-uptake blockade. However, this did not correlate with clinical response to longer-term SSRI treatment
The interrelatedness of book selection and censorship in public libraries with special reference to the position in the Republic of South Africa
No full textBibliography: leaves 214-243.The thesis approached the investigation as to whether or not there is any interrelatedness between book selection and censorship in public libraries , in two ways : viz.(a) a review of the literature, and (b) an exploratory empirical investigation of the position in South Africa. The literature survey was the major part of the study in which the attention was focused on the current position in the United Kingdom, the United States of America and the Republic of South Africa. As a means of introduction to the public library, a brief outline of the rise of libraries in the West was given, with special mention being made of the growth of literacy. The modern public library's aims and objectives in the three countries concerned were covered separately as these determine the formulation of a specific book selection policy. This in turn depends on two main factors, viz. the nature of the community being served and the theoretical principles of book selection. The possible negative effects of literary censorship on public libraries, realising their aims and objectives, is discussed by first giving an outline of literary censorship in the West. This is preceded by a discussion of the pros and cons of censorship which served as an introduction to the issue as• to whether or not censorship occurs in public libraries by examining such aspects as their assumptions, the response to complaints, and the reserve shelf. The empirical study served as a corollary to the above. It covered all the public libraries in South Africa which determine selection policy to any large extent, viz. the four provincial library services and the then autonomous municipal libraries. The rudimentary nature of the study resulted in no definitive statements being made. Nevertheless, it appeared that as their overseas counterparts , South African librarians did sometimes censor. It was concluded that all librarians sometimes censor so that there is an interrelatedness between book selection and censorship
Gone with the shining things
No full textIncludes bibliographical references.The lure of gold in the great reefs of Johannesburg near the end of the 19th century not only attracted the famous mining barons such as Cecil John Rhodes, Alfred Beit and Barney Barnato: working men also came from far and wide to feed their families with their labour. Among them was my great-grandfather, the miner from the Isle of Man, William Cogeen. He arrived via the tin mines of Cornwall and the silver mines of Colorado, and was among those Uitlanders who flocked in those early days to the Transvaal as skilled artisans - wheelwrights, farriers, bricklayers and, especially, experienced hard-rock miners. It was their labour, as well as of black tribesmen from all over southern Africa, that laid the financial foundation for what became the rich city of Johannesburg. It was also their influx that was the excuse that precipitated the Anglo-Boer War. His wife and daughters joined him in what was still a rough boom town, and they stayed on, until forced to flee as refugees from Johannesburg at the start of the war in 1899. Intrigued by the stories my mother and grandmother told me as a child, I began to research my family’s history and travelled to the Isle of Man, Cornwall and Colorado to trace their origins - and my own. This is the remarkable story of what happened to an ordinary working-class family who lived in extraordinary times, and my journey in their footsteps
Designing 21st Century Standard Ware: The Cultural Heritage of Leach and the Potential Applications of Digital Technologies
No full textThis practice-based research investigates the potential applications of digital manufacturing technologies in the design and production of hand-made tableware at the Leach Pottery. The methodology for the research establishes an approach grounded in my previous experience as a maker that is informed by an open, experimental, emergent, and responsive framework based on Naturalistic Inquiry.
A critical contextual review describes the cultural heritage of Leach which, for the purposes of the research, is developed through the Leach Pottery as a significant site, the historical production of the iconic Leach Standard Ware and the contemporary production of Leach Tableware. This is followed by an examination of Potter’s Tools in the Leach production environment, and a review of makers’ digital ceramic practice.
The contextual review is followed by an explication of ‘standards’ presented through visual lineages of Standard Ware and Leach Tableware to define ‘standard’ at a design (macro) level, followed by an examination of how ‘standard’ operates at a making (micro level) level. This chapter presents new knowledge in relation to defining the visual field of Leach Pottery tableware production and its standards of design.
A chapter focussed on practice presents the outcomes and analysis of my engagement with digital manufacturing technologies which resulted in the development of new tools to support Leach Tableware production and the interrogation of Leach forms, in different mediums, which led to the creation of Digital-Analogue Leach forms. The practice culminated in the design and development of new 21st century Standard Ware: a range of 9 forms, called Echo of Leach, that were developed by myself using digital and analogue methods: the designs were realised by myself, the Leach Studio, and a further four makers. The outcomes of the research were presented in a three month exhibition at the Leach Pottery in 2013.
The conclusions of the research draw on the key points raised in the analysis of the practice and relate these to the approaches to making pottery that are highlighted in the cultural heritage of Leach in the contextual review. These are also discussed in relation to ways in which these findings could be taken forward into development of knowledge about Standard Ware, especially in a broader studio pottery context
Translating men : humanism and masculinity in Renaissance renditions of patristic texts
No full textPhDThis doctoral thesis focusses upon the translation of patristic works into English in
the sixteenth and seventeenth centuries. Considering the pragmatic usage of texts in humanist
culture, this research project explores the mobilisation of vernacular versions of the Church
Fathers in response to historical crises. Regarding Renaissance humanism as a gendered
intellectual methodology,I have investigated the way in which these texts particularly aim to
address the needs of men, offering them exemplars to 'cope' with their social circumstances.
The first chapter involves the analysis of Thomas Drant's rendition of Gregory of
Nazianzus' Epigrams (1568) as part of the struggles of the early Elizabethan era. I suggest
that this verse translation may possibly have played a supportive role for Protestant clerics
facing a loss of humanist confidence due to educational deficiencies and the conflict of
learning with the Catholic Louvainist scholars.
The second chapter examines John Healey's version of Augustine's City of God
(1610) in the context of the colonisation of Virginia. I propose that the Augustinian text - and
the included commentary by Vives - may have represented a 'handbook' for the
predominantly male community of planters confronted by (among other problems) the severe
difficulty of establishing a household and fathering the next generation.
The third chapter looks at Tobie Matthew's translation of Augustine's Confessions
(1620) as an aid for Catholic Englishmen in an age of religious persecution. I contend that
this text advertises and advances a passive / feminine form of manhood - which had been
initially propagated by late sixteenth-century recusant ideology - in order to offer succour to
its socially debilitated male readers.
By undertaking an examination of these previously neglected texts, this thesis has
attempted to expand the understanding of Renaissance humanist translation, as well as to
offer a unique insight into the history of gender
Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A new anti-mycobacterial class that targets mycobacterial energy metabolism
No full textPhenotypic whole-cell high throughput screening of a library of small polar molecules led to the identification of a phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing the ester moiety with a methyl oxadiazole bioisostere. A route utilizing polymer-supported reagents was designed and executed to explore structure activity relationships with respect to the N-benzyl substituent, leading to compounds with nanomolar activity against Mycobacterium tuberculosis. The frontrunner compound (5h) from these studies was well tolerated in mice. A M. tuberculosis cytochrome bd oxidase deletion mutant (∆cydKO) was hyper-susceptible to compounds from this series, and a strain carrying a single point mutation in qcrB, the gene encoding a subunit of the menaquinol cytochrome c oxidoreductase (bc1 complex), was resistant to compounds in this series. In combination, these observations indicate that this novel class of anti-mycobacterial compounds inhibits the cytochrome bc1 complex, a validated drug target in M. tuberculosis.
Author list: Renier van der Westhuyzen, Susan Winks, Colin R. Wilson, Grant A. Boyle, Richard K. Gessner, Candice Soares de Melo, Dale Taylor, Carmen de Kock, Mathew Njoroge, Christel Brunschwig, Nina Lawrence, Frik Sirgel, Paul van Helden, Ronnett Seldon, Atica Moosa, Digby Warner, Luca Arista, Srinivasa Rao, Ujjini H. Manjunatha, Paul W. Smith, Leslie J. Street, Kelly Chibal
Honors in Practice, Volume 20, 2024
No full textGuest Editor’s Introduction • John Zubizarreta
Remebering Ada Long
A Long Legacy for the Ages (Dedicatory Essay) • Jeffrey A. Portnoy
Keep Ada Happy! • Larry Andrews
Honors in Practice: Ada Long • Bernice Braid
Tribute to Ada Long • James J. Clauss
For Ada • Lisa L. Coleman
Memories of Ada—With Fondness and Admiration • Kevin W. Dean
Reflections on Ada Long • Joan Digby
Life, Love, Work, and Ada Long • Linda Frost
Insight, Sincerity, and Wit: Remembrances of Ada • Galit Gertsenzon
Giant Shoes to Fill • Devon Graham
Not All Heroes Wear Capes—Remembering Ada Long • Raymond Green
An Author’s Note about the Editor • Annmarie Guzy
My Friend Ada • Jerry Herron
Acknowledging Editor Ada Long • Mimi Killinger
Ada Long’s Honors Program: From Dream to Memorable Reality • John A. Knox
In Remembrance: Ada Long • George Mariz
The Adoration of Ada • Mitch Pruitt
Ada as LegendMitch PruittHonors Pedagogy, the Pioneering Spirit, and What We Owe the Future • La Tanya L. Reese Rogers
Be Like Ada! • Rae Rosenthal
My Octopus Director • Rusty Rushton
Reflections • Chris Simon
Ada Long: A Servant Leader in Honors • Michael E. Sloane
When I Met Ada • Michaela Ruppert Smith
I Wouldn’t Say I Ever Met Ada • Christopher J. Syrnyk
My Experience in Honors with Dr. Ada Long • Maria V. Tarasova
I See Her Laughing • Norm Weiner
About the Contributors to “Remembering Ada Long”
2023 Presidential Address
A Year of Great Change and a Future of Greater Change • Susan E. Dinan
Letter
Partners in the Parks: A Shirt Tale • Joan Digby
Essays
Toward Student Success: The Impact of Honors Participation on Transfer Student Graduation Rates • Judy Albakry
A Matter of Definition, Criteria, and Standards in Honors: A History, from the Basic Characteristics to the “NCHC Shared Principles and Practices of Honors Education” • Richard Badenhausen and James Buss
Partners in Peace: A Sketch for a Link between the Nobel Peace Prize and NCHC • Kevin W. Dean and Henrik Syse
Mindfulness in Honors: An Experiment in Collaborative Learning and Team Teaching • Pascale F. Engelmajer and Massimo A. Rondolino
Addressing the Climate Crisis through Science and Art: The Value of Interdisciplinary and Intergenerational Team Teaching • Megan Jacobs and Kineo Memmer
If They Build It, They Will Come: The Power of Student-Designed Honors Offerings in Small-Budget Programs • Claire H. Procopio
Forming Civic Virtue through an Honors Seminar Focused on Local Civil Rights History • Lynn Stallings and Aaron D. Cobb
Third-Year Medical College Rotations for Premedical Honors Program Undergraduates • Harvey G. Stenger, Jr., and William L. Ziegler
Creating a Diverse Honors Faculty through Collaborative Relationships within the Community and the University • Amelia Underwood, Philip L. Frana, and Fawn-Amber Montoya
“We Advocate a Semi-Revolution”: An Honors Conference Undergoes Transformation • Betsy Greenleaf Yarrison and Bruce Thompson
Brief Ideas about What Works in Honors
The Involvement Journal: A Signature First-Year Seminar Assignment • Matt Baran
Teaching Honors Leadership Courses with Relevance • Jean-Paul Benowitz
Aristotle’s Poetics: A Biologist’s Approach to Tragedy • James J. Clauss
Fostering Belonging through Bread (and Other Foods) • Maria Elliott and Steve Garrison
Physics and Theatre: An Unexpected Pairing that Enhances Learning for Both Disciplines • Amber Karlins
The Honors Research Project: Embracing Intellectual Discovery through Storytelling • Malachi D. Crawford, Chelsee B. H. Young, Kimberly Michelle Gay, and Quincy C. Moore
Interdisciplinary Cohort Building: Creating a Feeling of Belonging and Sense of Community in Honors Transfer Students • Shannon Pittman and Vanessa Miller
Food and Culture • Brigett Scott
About the Author
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