Shaded Boxes Research Articles

777. Implementation of Antimicrobial Impregnated Catheters to Reduce Central Line Associated Bloodstream Infections (CLABSI) in a Pediatric Setting

BackgroundAntimicrobial impregnated catheters (AIC) are one strategy to prevent CLABSI with existing data for central lines required for short duration, however, the strength of evidence, particularly for children, is lacking. Recent 3-year CLABSI data at our institution show 60 (51%) infections occurred in central lines within 8 weeks of insertion, suggesting an opportunity for evaluation of an intervention targeting this time frame. We implemented AIC to evaluate their effectiveness in reducing CLABSI standardized infection ratio (SIR) in patients requiring central venous access for less than 8 weeks. We also monitored for complications (malfunction, line exchange, fungal infection).MethodsA stepped wedge observational design was used to implement Minocycline + Rifampin impregnated catheters in a rolling fashion across the institution. Children > 3kg were eligible if admitted to a participating unit and required central venous access through a peripherally inserted central catheter (PICC), non-tunneled catheter, or tunneled non-cuffed femoral catheter for < 8 weeks. Units, prioritized based on CLABSI SIR, were added to the intervention monthly until AIC were used throughout the institution. A multidisciplinary team (infectious diseases and infection control experts, CLABSI leaders, unit-based physicians and nurses, proceduralists, supply chain) met weekly to facilitate implementation, assess for CLABSI and monitor for complications.Figure 1. Study design. This figure describes the stepped wedge study design where units were phased into the invention on a rolling monthly basis allowing for comparison between and within units. The shaded boxes represent time periods when units were using antimicrobial impregnated catheters and the white boxes represent time periods when units were using standard non-impregnated catheters.ResultsAIC were systematically implemented over a 7-month period. The institution’s CLABSI SIR decreased from 0.80 to 0.59 during this timeframe. There were no NHSH defined CLABSI in patients with an AIC during the intervention. Obstacles included shortage of catheters due to supply chain disruption, adjustment of technique for line insertion and cracked/broken lines. Infections and complications were reviewed by the multidisciplinary team and compared to historical rates with non-impregnated lines. This figure shows the institution’s rolling 12-month SIR during the intervention period.ConclusionCLABSI SIR decreased at our institution during the intervention period. While many efforts likely led to this reduction (optimizing maintenance bundle, unit based CLABSI initiatives), we believe the use of AIC contributed to this improvement. There were no pediatric-specific safety events identified during implementation.Disclosures Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial stipend as Co-EiC, Clinical Therapeutics)Hologic (Consultant)Seqirus (Consultant)

Correction for Balamurugan et al., "Cross-Reactivity against Multiple HIV-1 Epitopes Is Characteristic of HIV-1-Specific Cytotoxic T Lymphocyte Clones".

Volume 92, no. 16, e00617-18, 2018, https://doi.org/10.1128/JVI.00617-18. Page 5: In Fig. 2, there was a transposition error of the shaded boxes in the lower left (B*40) panel. The shading should have indicated recognition of the index epitope IL9 (Pol 357-365) and cross-recognition of the KL9 epitope (Gag 481-489).

Effectiveness of shading to mitigate the impact of high temperature on sea turtle clutches considering the effect on primary sex ratios

Developmental success of sea turtle clutches depends on incubation temperature, which also determines sex ratio of hatchlings. As global temperatures are rising, several studies have proposed mitigation strategies such as irrigation and shading to increase hatching success. Our study expands upon this research and measures the effects of using boxes with different degrees of shade coverage (50%, 80%, and 90%) on sand temperature and water content. Boxes were fully covered with fabric in 2017/2018 (top and sides) but were side open in 2018/2019. We took measurements at olive ridley (Lepidochelys olivacea) and leatherback (Dermochelys coriacea) turtle nest depths (45 and 75 cm) at Playa Grande, Costa Rica. Shading reduced temperature by up to 0.8 °C and up to 0.4 °C at 45 cm and 75 cm, respectively. There were statistically significant differences between shading and control treatments at both depths, but differences between shade treatments were only significant when using side open boxes, possibly due to air flow. Shading had no effect on water content. While the impact of using shaded boxes on temperature was low, the potential impact on primary sex ratios was large. If shading were applied to leatherback clutches, the percentage of female hatchlings could vary by up to 50%, with a maximum difference around the pivotal temperature (temperature with 1:1 sex ratio). Shading can be useful to increase hatching success, but we recommend avoiding it at temperatures within the transitional range (temperatures that produce both sexes), or using it only during the last third of incubation, when sex is already determined. As global warming will likely continue, understanding potential impact and effectiveness of mitigation strategies may be critical for the survival of threatened sea turtle populations.

A History of Russian Literature by Kahn Andrew (review)

Slavonic and East European Review, 98, 1, 2020 Reviews Kahn, Andrew; Lipovetsky, Mark; Reyfman, Irina and Sandler, Stephanie. A History of Russian Literature. Oxford University Press, Oxford and New York, 2018. xix + 939 pp. Illustrations. Guides to further reading. Notes. Index. £69.00: $93.00. Happily, as we flounder about today at the mercy of too much auto-assembled information, the consciously authored literary history is flourishing. In humanities publishing, the market is healthy for both overviews and what might be called ‘underviews’. Each has its strengths and risks. An overview — such as the volume discussed here — is the comprehensive chronological story: fine-grained thick description, broad horizons, the slow crawl along the wide road with luxurious excursions into political and social context, all in one massively overweight tome. It co-exists in the field with the immensely popular underview: skinny underweight series paperbacks with such titles as Russian Literature: A Very Short Introduction (Oxford, 2001) or Russian Literature: A Brief Insight (New York, 2010), in this instance both by Catriona Kelly and each built around Alexander Pushkin. Both long and short variants of historical viewing assume that wisdom in the humanities is not just mechanical or accretive (that is, not googled, tweeted or blogged) but takes time to think through. To aspire to historical wisdom is to be integrated, visionary, ‘voiced’, and willing to take risks and stands that endure beyond the passing moment. The special vulnerability of ‘very-shorts’ and ‘brief insights’ is their authorship by experienced individual minds, whose synthesizing brilliance compensates for all compressions and omissions. It is easy and pleasant to absorb such stripped-down, artful profiles of a literary tradition — and tiny single-authored surveys, which can inadvertently create new norms by their very elegance and quotability, are read as much for the author as for the subject matter. The vulnerability of the lengthy contextualized overview lies elsewhere. Today, any in-print survey pretending to fullness can be instantly outdated. All academic fields are under pressure to be constantly open to shifting global perspectives and previously unheard voices. Can even the most meticulous hard-copy linear narrative hope to keep up with these challenges? In my view, the new Oxford History of Russian Literature, a staggering accomplishment, manages to do so. This review suggests some reasons why. Generically, the Oxford History is a massive, multi-authored overview, supplemented by select under-views. Its overall structure is chronological, in five parts: ‘The Medieval Period’ (from the origins of writing through the end of the sixteenth century); ‘The Seventeenth Century’ (the literary fallout of the Church Schism followed by the embattled advent of humanism in theatre, REVIEWS 153 poetry and prose); ‘The Eighteenth Century’ (imported classicism, the rise of national narratives and satire); ‘The Nineteenth Century’ (with close attention to social classes, literary types, women writers and evolving readerships — but not tightly tethered to the old Romanticism-to-Realism model); and finally ‘The Twentieth and Twenty-first Century’ (in one unified sweep, with Soviet Communism tucked in between two freer, more experimental eras). Within each part, however, movement and mutual causation are more lateral than linear or temporal, more of a mesh than a ribbon. Official institutions mould writers,butviceversatoo;thehistoryofRussiansyllabicsandthensyllabotonics is in dialogue with the differing rules of Polish and Ukrainian versification. Thematic anchoring is provided by keywords (baroque, sobornost´, nihilism, skaz) and by the occasional topical under-view: a ‘case study’ set off in a shaded box. These case studies vary in length from a paragraph to several pages. Some are devoted to persons (Gogol´, Petrushevskaia, Elena Shvarts, Nabokov — for writers who fled Russia or were exiled are integrated into the fabric, not given a lens of their own). Other shaded boxes discuss objects (albums), processes (word-weaving, corporal punishment, the prorabotka or ‘political rebuke’), institutions (the Moscow-Tartu School), individual works (Lay of Igor’s Campaign, Prigov’s ‘Militsaner’), or a combination of persons, processes and texts (Leo and Sofia Tolstoi as diary-writers). A gorgeous inlay of colour illustrations begins with a leaf from the eleventh-century Ostromir Gospel, passes through regal portraiture and modernist design, and ends with Komar and Melamid’s Origin of Socialist Realism, a parodic icon featuring Joseph...

253 Geographic Early-Onset Colorectal Cancer Incidence Rate Disparities Within White and African American Populations in the United States

INTRODUCTION: Prior study by our group revealed marked geographic disparities in early-onset colorectal cancer (EOCRC) incidence rates (IR) (Abualkhair et al. abstract #984 DDW 2019). Although it is established CRC IRs in African Americans are higher than whites, there is paucity of data on geographic EOCRC disparities within both white and African American populations. Hence, we seek to explore the role race may play in IR differences between U.S. regions and individual registries. METHODS: 2000–2015 SEER 18 CRC IR Analysis (170,434 cases) was performed in one-year age increments (ages 30–60) in four U.S. regions, individual registries and stratified by race. RESULTS: There are wide regional IR disparities at multiple ages within both white and African American populations. For example, at age 45, there is a 52% difference (P &lt; 0.05) between the highest (south) and lowest (west) regional IRs in African Americans compared to a 32% difference (P &lt; 0.05) in whites (Figures 1 and 2). At multiple age points &lt;50, there is a trend for greater disparity between the highest and lowest regional IRs within the African American population compared to within the white population (shaded boxes in Figure 2) however these did not reach statistical significance at most ages. CONCLUSION: There are marked geographic EOCRC IR disparities within white and African American populations between U.S. regions. There appears to be a trend toward more pronounced geographic disparities within the African American population, however interpretation is limited by lack of statistical significance at multiple age points, likely due to lower case counts. Targeting all populations is critical for CRC prevention, however we must assure attention is paid to higher-risk populations. Potential interventions include targeted risk factor modifications, assuring concerning symptoms trigger prompt diagnostic evaluations and taking advantage of earlier age 45 screening options supported by some guidelines (USMSTF recommends screening African Americans at age 45 and ACS recommends average-risk screening of all patients at age 45). By identifying higher-risk populations, future targeted studies can also be performed which may allow better understanding of rising EOCRC rates.

Modeling the effect of the cephalic phase of insulin secretion on glucose metabolism

The nervous system has a significant impact in glucose homeostasis and endocrine pancreatic secretion in humans, especially during the cephalic phase of insulin release (CPIR); that is, before a meal is absorbed. However, the underlying mechanisms of this neural-pancreatic interaction are not well understood and therefore often neglected, despite their significance to achieving an optimal glucose control. As a result, the dynamics of insulin release from the pancreas are currently described by mathematical models that reproduce the behavior of the β cells using exclusively glucose levels and other hormones as inputs. To bridge this gap, we have combined, for the first time, metabolic and neural mathematical models in a unified system to reproduce to a great extent the ideal glucoregulation observed in healthy subjects. Our results satisfactorily replicate the CPIR and its impact during the post-absorptive phase. Furthermore, the proposed model gives insight into the physiological interaction between the brain and the pancreas in healthy people and suggests the potential of considering the neural information for restoring glucose control in people with diabetes.Graphical (a) Physiological scenario. Diagram of the biological interaction among the most important organs involved in glucose control during meal intake. (b) Scheme of the unified bio-inspired neural-metabolic model. Each of the boxes represents one subsystem of the model. The pink shades boxes depicts the novel subsystems introduced to the current metabolic models (grey shaded boxes). Insulin-related action and mass fluxes (solid black lines) and glucose-related action and mass flux (dotted black lines) are depicted to show the relationship among the blocks. I(t), Ic(t), G(t) and SI related to plasma insulin, plasma cephalic insulin, plasma glucose and insulin sensitivity, respectively.

IMPLEMENTATION OF AN ELECTRONIC PRESCRIPTION CHART FOR GENTAMICIN FOR NEONATAL UNITS AND POSTNATAL WARDS

AimSince the introduction of NICE guidance for Early Onset Neonatal Sepsis (EONS)1 in August 2012, the number of locally reported prescribing and administration errors involving gentamicin has increased. This guideline...

Spanish Fiction in the Digital Age: Generation X Remixed by Christine Henseler (review)

Reviewed by: Spanish Fiction in the Digital Age: Generation X Remixed by Christine Henseler Roberta Johnson Spanish Fiction in the Digital Age: Generation X Remixed. Palgrave Macmillan, 2011. By Christine Henseler. Imagine a book that provides a detailed account of the fiction by so-called Generation X writers and post-Generation Xers (my term, not Henseler’s) while at the same time giving you a hands-on feel for the porous, interactive aesthetics in which the writers engaged. Spanish Fiction of the Digital Age: Generation X Remixed is such a book. Christine Henseler’s imaginative, collaborative, remixed text assays a new kind of literary criticism in which the scholar participates in an ongoing dialogue with other scholars, with the fiction writers, and with herself. Henseler includes sidebars (in shaded boxes) on nearly every page that contain responses to her ideas from other critics and from the authors she analyzes, as well as pertinent material from and links to the Internet. This practice upends typical academic quotations, which are filtered through the author’s viewpoint to bolster an argument. Henseler’s discussion exists on the same plane as comments by others without reducing them to a single point of view. It is perhaps the closest one could come in the traditional print media to an interactive chat room, simulating what some writers attempted to achieve in their fiction: “it is through non-traditional means such as blogs, literary magazines, videos, or fanzines that Mutantes must insert their critical voices and break down barriers between authors, readers, and critics” (Henseler 152). Amazingly, Henseler accomplishes this feat without sacrificing sound scholarship. Spanish Fiction of the Digital Age is exceptionally well researched. Henseler knows the primary literature (not only in Spanish but in other languages—particularly English and German), the secondary literature, and a great deal about the media (MTV, video games, the Internet, and reality TV) that underpin the aesthetics of a sector of recent Spanish fiction. She cites all the significant bibliography on Generation X, such as Cristina Moreiras Menor’s Cultura herida: Literatura y cine en la España democrática, whose final chapter is devoted to the phenomenon, Carmen Urioste’s Novela y sociedad en la España contemporánea (1994–2009), which covers the same period from a more socio-political perspective, and the seminal articles included in Generation X Rocks: Contemporary Peninsular Fiction, Film, and Rock Culture that Henseler edited with Randolph Pope. Henseler’s own approach is more akin to Eva Martínez Navarro’s La novela de la Generación X, which “examined the role of television, video, and music on Gen X novels’ themes, structures, and parameters” (Henseler 3). Henseler’s interpretation of Spanish fiction in the digital age draws on these sources, but she deepens our understanding of how new technological media function and how writers with similar experiences with this media differ significantly in their literary appropriation of it. She makes an important distinction between “early” Generation X writers, like José Ángel Mañas and Ray Loriga, the so-called “dirty realists” who focus on drugs and rock and roll, and a later group, for which she suggests several names: “the ‘Nocilla Generation’ based on Agustín Fernández Mallo’s trilogy Nocilla Dream (2006), Nocilla Experience (2007), and Nocilla Lab (2009); the “After-Pops,” in line with Eloy Fernández Porta’s much acclaimed critical work in After-Pop: la literatura de la implosión mediática (2007); and the term [she] prefer[s], the “Mutantes,” as best expressed in the short story volume Mutantes: Narrativa española de última generación (2007), coedited by Juan Francisco Ferré and Julio Ortega” (8). The latter are more cosmopolitan and project a less pessimistic view of life and media than the earlier writers. The book is divided into six chapters that follow a chronological format. Most center on a particular media phenomenon with an in-depth analysis of one work that exemplifies it. Chapter one surveys the history of the term Generation X. Chapter two focuses on the background to José Ángel Mañas’s (by most accounts) watershed Historias del Kronen, including La Movida, Punk, and Avant-Pop, to conclude that Historias is...

Understanding Socioeconomic and Racial/Ethnic Status Disparities in Diet, Exercise, and Weight: Underlying Contextual Factors and Pathways

Understanding Socioeconomic and Racial/Ethnic Status Disparities in Diet, Exercise, and Weight: Underlying Contextual Factors and Pathways

Cause-specific mortality adjudication in the UPLIFT® COPD trial: Findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

DENN Domain Proteins: Regulators of Rab GTPases

The DENN domain is a common, evolutionarily ancient, and conserved protein module, yet it has gone largely unstudied; until recently, little was known regarding its functional roles. New studies reveal that various DENN domains interact directly with members of the Rab family of small GTPases and that DENN domains function enzymatically as Rab-specific guanine nucleotide exchange factors. Thus, DENN domain proteins appear to be generalized regulators of Rab function. Study of these proteins will provide new insights into Rab-mediated membrane trafficking pathways.

Corrigendum to ‘The use of roflumilast in COPD: a primary care perspective’ (Prim Care Resp J 2010;19(4) (Suppl 2):342–351)

The authors regret that an error occurred in Figure 3 on page 349, which has already been corrected in the online version of the paper: The text in the first two shaded boxes on the left-hand side of the Figure read At risk Mild • FEV1/FVC <0.70 • FEV1/FVC <0.70 • FEV1 ≥80% predicted • 50% ≤ FEV1 <80% predicted and should read At risk Mild • FEV1/FVC ≥0.

Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs

Resorcylic acid lactones are fungal polyketides that display diverse biological activities, with the potent Hsp90 inhibitor radicicol being an important representative member. Two fungal iterative polyketide synthases (IPKSs), Rdc5, the highly reducing IPKS, and Rdc1, the nonreducing IPKS, are required for the biosynthesis of radicicol in Pochonia chlamydosporia. In this study, the complete reconstitution of Rdc5 and Rdc1 activities both in vitro and in Saccharomyces cerevisiae uncovered the earliest resorcylic acid lactone intermediate of the radicicol biosynthetic pathway, (R)-monocillin II. The enzymatic synthesis of (R)-monocillin II confirmed the exquisite timing of the Rdc5 enoyl reductase domain. Using precursor-directed biosynthesis, the chemical modularity of the dual IPKS system was determined. Rdc1 readily accepted an N-acetylcysteamine thioester mimic of the reduced pentaketide product of Rdc5 to synthesize (R)-monocillin II with four additional iterations of polyketide elongation, indicating the C2' ketone group found in (R)-monocillin II is incorporated via the functions of Rdc1 instead of Rdc5. The involvement of the thioesterase domain in Rdc1 in macrolactonization was confirmed through both site-directed mutagenesis and domain deletion. The Rdc1 thioesterase domain was also shown to be tolerant of the opposite stereochemistry of the terminal hydroxyl nucleophile, demonstrated in the precursor-directed synthesis of the enantiomeric (S)-monocillin II. Finally, reconstitution of the halogenase Rdc2 was demonstrated both in vivo and in vitro in the synthesis of pochonin D and a new halogenated analog 6-chloro, 7',8'-dehydrozearalenol.

Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation of Dronc

Apoptosis ensures tissue homeostasis in response to developmental cues or cellular damage. Recently reported genome-wide RNAi screens have suggested that several metabolic regulators can modulate caspase activation in Drosophila. Here, we establish a previously unrecognized link between metabolism and Drosophila apoptosis by showing that cellular NADPH levels modulate the initiator caspase Dronc through its phosphorylation at S130. Depletion of NADPH removed this inhibitory phosphorylation, resulting in the activation of Dronc and subsequent cell death. Conversely, upregulation of NADPH prevented Dronc-mediated apoptosis upon DIAP1 RNAi or cycloheximide treatment. Furthermore, this CaMKII-mediated phosphorylation of Dronc hindered Dronc activation, but not its catalytic activity. Blockade of NADPH production aggravated the death-inducing activity of Dronc in specific neurons, but not in the photoreceptor cells of the eyes of transgenic flies; similarly, non-phosphorylatable Dronc was more potent than wild type in triggering specific neuronal apoptosis. Our observations reveal a novel regulatory circuitry in Drosophila apoptosis, and, as NADPH levels are elevated in cancer cells, also provide a genetic model to understand aberrations in cancer cell apoptosis resulting from metabolic alterations.

Theorists of the Modernist Novel: James Joyce, Dorothy Richardson, Virginia Woolf (review)

Reviewed by: Theorists of the Modernist Novel: James Joyce, Dorothy Richardson, Virginia Woolf Eric Bulson (bio) Theorists of the Modernist Novel: James Joyce, Dorothy Richardson, Virginia Woolf, by Deborah Parsons . New York: Routledge Publishers, 2007. 176 pp. $23.95. Literary guidebooks abound nowadays. Every major publisher, it seems, has a separate series created specifically for the general reader and curious student eager for a no-nonsense sourcebook. Over the past decade, Routledge has created a number of different series, all of them intended to make legendary critical thinkers from twentieth-century philosophy and literature accessible to a wider audience of non-specialists. Compact guides to Fredric Jameson, Gilles Deleuze, Michel Foucault, Edward Said, and Gayatri Chakravorty Spivak are all there, along with a few others organized by subject: cyberculture, film theory, modernist poetry, and the modernist novel among them. These pocket-size volumes in the Routledge Critical Thinkers series (they rarely have more than 170 pages) are often found in a single carousel at the bookstore, with an array of brightly colored covers meant to attract the attention of passing customers. There's the lime green of Homi Bhabha, the moody purple of Theodor Adorno, the grey shades of Paul de Man, and the post-apocalyptic orange tones of Stuart Hall. One cover, one color is never enough. These guidebooks are meant to be collected, maybe even traded like baseball cards, and they have the power to brighten even the most dismal-looking bookshelf. Deborah Parson's Theorists of the Modernist Novel: James Joyce, Dorothy Richardson, Virginia Woolf is an excellent contribution to this series. In fact, while I have found over the years that these guides can be hit or miss, this one does an amazing job precisely because it manages to prepare readers without taking the sense of discovery away. There are certainly going to be the lazy ones who read introductions to the modernist novel precisely to avoid reading modernist novels, but for others, who are motivated enough to see an introduction as a point of departure, the rewards will be well worth it. Parsons is the kind of guide you want for an introduction of this sort: clear, focused, balanced, learned, and attuned to her audience's needs. There is an energy in these pages that comes from the depth of her knowledge about the subject and her ability to convey information without getting bogged down by too many qualifications, diversions, and non-essential factoids. Scattered throughout each [End Page 469] chapter are shaded boxes containing keywords with definitions that every reader will need at some point. Some of them are obvious, but there are others here—"angel in the house," "moments of being," "Mr. Bennett and Mrs. Brown," "epiphany"—that consolidate major modernist issues and concepts. Theorists of the Modernist Novel, as the title itself suggests, is not meant to be an exhaustive guide to any single author. In fact, it stands out from what is already on the market precisely because of the thematic organization. Instead of making Joyce or Woolf or Richardson representative of an entire genre or period, Parsons emphasizes their differences, specifically as they relate to new forms of realism, the representation of character and consciousness, gender, and time. For that reason, readers will see that the modernist novel was not some pre-made, monolithic genre. It had to be invented or adapted, and the results, as we see from the novels of Joyce, Woolf, and Richardson, were often radically different. All three novelists struggled to represent modern life, but their solutions were varied, and Parsons makes us see how, when read together, they were experimenting with narrative, language, and the form of the novel itself to capture something real, maybe even true, about the world around them. The representation of consciousness was one of the places where the modernist novel broke forcefully from its realist predecessor, and Parsons shows us how the modernist interest in a psychological realism drove formal experimentation. Joyce, Woolf, and Richardson developed techniques that would allow them to get into the heads of their characters, but they did not do it the same way or with the same results. Joyce preferred full immersion in a few...

The Hairless Phenotype of the Hirosaki Hairless Rat Is Due to the Deletion of an 80-kb Genomic DNA Containing Five Basic Keratin Genes

Most models of hereditary hypotrichosis are due to alterations in growth factors and transcription factors, and the examples of causative mutations in hair keratin genes are limited. The Hirosaki hairless rat (HHR) is a mutant strain spontaneously derived from Sprague-Dawley rats (SDRs). In this study, the locus of the responsible gene was examined by linkage analysis and mapped on chromosome 7q36. Because many basic keratin genes are clustered on 7q36, their expression was examined. Reverse transcription-PCR and genomic PCR indicated that the Kb21 (Krt81), -23 (Krt83), and -26 (Krt86) genes encoding basic hair keratins were not expressed and were deleted. Furthermore, 80-kb genomic DNA ranging from exon 9 of Kb25 (Krt85) to exon 9 of Krt2-25 was deleted. The breakpoints of these genes were within a 95-bp portion shared by the two genes, suggesting that deletion due to non-allelic homologous recombination occurred. Proteins identified as Kb21, Kb23, and Krt2-25 in SDR hairs by mass spectrometry were not detected in HHR. Instead, the product of a fusion gene became dominant in HHR. Because fusion occurred between the exons of the two genes with the same sequences, the product was identical to the wild-type Kb25 protein. By using immunohistochemistry, Kb21 was not detected in HHR hair follicles. Kb25 was expressed in the cortex in HHRs, whereas it was in the medulla in SDRs. This study clearly illustrates the importance of hair keratin genes in hair growth.

Nursing Leadership

Nursing Leadership Shaw, Sally , 2007 ; International Council of Nurses/Blackwell Publishing : 215 pages. Paperback (ISBN : 978-1-4051-3523-8 ). Nursing Leadership provides an invaluable guide on developing leadership knowledge and skills, together with an evaluation of the International Council of Nurses' (ICN) Leadership for Change (LFCTM) programme as implemented in more than 50 countries. The author Sally Shaw led the LFCTM programme for almost a decade from when it was first implemented in 1995. The LFCTM programme was developed in response to the global need for nurses to understand the ‘context and purpose of health care reform; (to have) a vision of how nursing and health care may develop in their countries; (to be able) to plan strategically and to manage change; and the strength and confidence to be proactive and fully involved in a challenging and often stressful change environment’ (page 22). With her vast experience of leading nurses through this programme in many different health care contexts, Shaw is well placed to draw on numerous real-life examples in support of the lessons she conveys. The examples are situated strategically in shaded boxes throughout the book. In the penultimate chapter, five case studies are presented that illustrate the return on investment of implementing the LFCTM programme in very different settings. Shaw herself leads the reader through the 11 chapters of Nursing Leadership in a process that develops from its focus and content, to the challenge of change, the nature of leadership (what it is and what it is not), the environment(s), designing a programme, the followers, mentoring, the ‘soul’ of leadership, outcomes for the individual and the setting, sustaining leadership and long term impacts, defining success, and making a difference. Nursing Leadership is therefore not only a highly readable account of a practical programme for nurse leaders and educators alike, but also a personal biography of how this was achieved and the responses of many of those involved with Shaw as she took the lessons of LFCTM around the world. Of course, the case studies and examples are all anonymous, although many of the countries from which they are drawn are named. At the recent ICN biennial conference in Yokohama, I was inspired by many of the nurses who made presentations at workshops on a variety of themes and issues initiated and supported by ICN. I have no idea whether those nurses had themselves participated in LFCTM. However, attending my fifth ICN conference in a row, I was struck by the growing self-confidence of so many of the nurses in what they had to report. It may be too far a stretch of the imagination to link that conference experience directly with the LFCTM programme. Yet I was left in no doubt that nursing is changing as nurses take control of sometimes desperate situations that might once have left them unsure of a strategy and possible courses of action. In many ways this is the real test of such a massive programme for change, which under the present leadership of Stephanie Ferguson, is now well into its second decade. Nursing Leadership is therefore much more than a teaching and learning tool, it is a reflection of the commitment and integrity of its author in taking forward ICN's own mission for developing nursing and health care globally. Some of the LFCTM outcomes can be empirically substantiated, others are much more diffuse. We do well to reflect on the wider impacts that programmes such as these have had, and are having, on nurses' leadership throughout the world. Needless to say, I strongly recommend Nursing Leadership to nurses everywhere involved in health care organisation, reform and change.

Meaningful Exchanges for People With Autism: An Introduction to Augmentative and Alternative Communication (Topics in Autism)

Cafiero JM. Bethesda, MD 20817, Woodbine House, 2005, paperback, 174 pp, illus, ISBN: 1-890627-44-5, $17.95. Written by a teacher in the public school system, this book provides an overview of augmentative and alternative communication (AAC) devices and is a useful resource for parents or professionals who are involved with children who have disabilities. The book is well conceptualized with a clear outline, case studies, vignettes, and numerous diagrams and photographs interspersed throughout the text. Key points are offset in shaded boxes, and small sections are devoted to helpful summaries like …

Modulation of D-Serine Levels via Ubiquitin-dependent Proteasomal Degradation of Serine Racemase

Mammalian serine racemase is a brain-enriched enzyme that converts L- into D-serine in the nervous system. D-Serine is an endogenous co-agonist at the "glycine site" of N-methyl D-aspartate (NMDA) receptors that is required for the receptor/channel opening. Factors regulating the synthesis of D-serine have implications for the NMDA receptor transmission, but little is known on the signals and events affecting serine racemase levels. We found that serine racemase interacts with the Golgin subfamily A member 3 (Golga3) protein in yeast two-hybrid screening. The interaction was confirmed in vitro with the recombinant proteins in co-transfected HEK293 cells and in vivo by co-immunoprecipitation studies from brain homogenates. Golga3 and serine racemase co-localized at the cytosol, perinuclear Golgi region, and neuronal and glial cell processes in primary cultures. Golga3 significantly increased serine racemase steady-state levels in co-transfected HEK293 cells and primary astrocyte cultures. This observation led us to investigate mechanisms regulating serine racemase levels. We found that serine racemase is degraded through the ubiquitin-proteasomal system in a Golga3-modulated manner. Golga3 decreased the ubiquitylation of serine racemase both in vitro and in vivo and significantly increased the protein half-life in pulse-chase experiments. Our results suggest that the ubiquitin system is a main regulator of serine racemase and D-serine levels. Modulation of serine racemase degradation, such as that promoted by Golga3, provides a new mechanism for regulating brain d-serine levels and NMDA receptor activity.

Novel Tumor Necrosis Factor-responsive Mammalian Neutral Sphingomyelinase-3 Is a C-tail-anchored Protein

Two genes encoding neutral sphingomyelinases-1 and -2 (sphingomyelin phosphodiesterases-2 and -3) have been recently identified that hydrolyze sphingomyelin to phosphorylcholine and ceramide. Data bank searches using a peptide sequence derived from a previously purified bovine neutral sphingomyelinase (nSMase) allowed us to identify a cDNA encoding a novel human sphingomyelinase, nSMase3, that shows only a little homology to nSMase1 and -2. nSMase3 was biochemically characterized by overexpression in a yeast strain, JK9-3ddeltaIsc1p, lacking endogenous SMase activity. Similar to nSMase2, nSMase3 is Mg2+-dependent and shows optimal activity at pH 7, which is enhanced in the presence of phosphatidylserine and inhibited by scyphostatin. nSMase3 is ubiquitously expressed as a 4.6-kb mRNA species. nSMase3 lacks an N-terminal signal peptide, yet contains a 23-amino-acid transmembrane domain close to the C terminus, which is indicative for the family of C-tail-anchored integral membrane proteins. Cellular localization studies with hemagglutinin-tagged nSMase3 demonstrated colocalization with markers of the endoplasmic reticulum as well as with Golgi markers. Tumor necrosis factor stimulates rapid activation of nSMase3 in MCF7 cells with peak activity at 1.5 min, which was impaired by expression of dominant negative FAN.