Linear Progression Research Articles

Author's Response

Author's Response Mark Massa SJ First, my sincere thanks to the three reviewers. It is always an honor to have one's scholarship taken seriously by scholars as smart as Rodger Van Allen, Christina Astorga, and John Grabowski. I'm delighted that the conversation about interpreting how (or whether) natural law "develops" continues in their responses to my book. My sense from the moment I started this project was that people would respond differently to it. So first: I'd like to offer a preliminary contextual observation before I get to the substance of the three reviews. The project that resulted in the writing of my book began during my final year as dean of the School of Theology and Ministry at Boston College. As anyone who has had the privilege of serving in an academic administrative position knows well, one has to build into one's day thirty or forty minutes of "non-decanal activity"—reading or writing that has nothing to do with budgets, bylaws, or personnel issues (if only to keep one's mental balance). Thus, during the 2015–16 academic year I disappeared from the dean's office every day for at least 30 minutes, without my cell phone (to the frustration of my superb administrative assistant) to bury myself in the stacks of the Theology and Ministry Library. The task I set for myself was to reread the books that, over the course of three decades, have shaped my life as a scholar. One of the most important of those works was Thomas Kuhn's landmark study in the history and philosophy of science, The Structure of Scientific Revolutions, a book I had read as an undergraduate in a philosophy of science course. The Jesuit community I lived in at the time included three moral theologians, two of them "virtue ethicians," and one of them an expert in Thomas and virtue ethics. How, I had been wondering for some time after our lively dinner conversations, did one make sense of the "development" of Christian morality if one set end-to-end Aquinas, Suarez, John Ford, Richard McCormick, Charles Curran, Germain Grisez, and Lisa Sowle Cahill? If one accepted all of them as theologians whose basic project was to offer smart "natural law" interpretations of the Catholic moral tradition, how might one understand the "development" of that tradition? Or was the word [End Page 72] "development" (a word that Kuhn himself tended to use in scare quotes when referring to the course of scientific research) perhaps the wrong one? The conclusion I came to was that it was indeed the wrong word unless one understood that there simply was no linear progression linking natural law discourse from Thomas to Humanae Vitae to Jean Porter. My narrative, in other words, takes as axiomatically true that Catholic moral theology has been marked by the same degree of disjunction, rupture, and discontinuity as Kuhn had discovered in studying the history of biology and physics. Successive models of natural law simply do not build on each other, despite the fact that most of them claimed be in the "Thomistic tradition" of natural law. And thus my book. Rodger Van Allen, with his usual and much-respected acuity, lucidly adumbrates the larger theme of my book: I had not set out to write a book about either birth control or the 1968 encyclical Humanae Vitae itself (both of which already have a number of superb studies in print, to which I direct the reader in my Introduction). Thus, it is no surprise my book is neither of those things. Rather, as Van Allen correctly notes, Humanae Vitae provides the occasion for pursuing a much larger (and in my opinion, more basic and more interesting) historical and epistemological question: how does Catholic theology "develop"? Or does it "develop" in anything like a linear, progressive, or organic manner (as several recent pontiffs have asserted—largely without proof, in my opinion). Or, in fact, is that word misused when talking about the history of Catholic theology? Thus, my book is more focused on tracing the morphology of change in Catholic theology than on the history of natural law theory per se. As Van...

Key Experimental Investigations of cutting dimensionality by Abrasive Water Jet Machining on Basalt Fiber /Fly ash Reinforced Polymer Composite

Abstract Abrasive water jet machining is a versatile in function to cut the extremely hard and inhomogeneous structured materials. Thermo set polymer matrix designed with multiple layer of hard rock fiber and fly ash rendered a high-performance structural material. The aim of the work is to investigate the cutting dimensionality of Basalt fiber/fly ash reinforced vinyl ester composite on abrasive water jet machining. Composite laminates -are prepared by multi stacking of basalt fiber with variation in fly ash particle loading (5-20 wt. %) using a compression molding technique. Improved mechanical properties of composites are obtained on varying the composition of fly ash. The linear progression of mechanical proprieties was limited by the agglomeration of fly ash particles. Mechanical properties enhancement is attributed to the polymer chain termination with fly ash particles leading to cross link density. The fracture mechanism and mode failure observed to be matrix cracking, particles crushing and brittle failure of fiber. Analysis of kerf dimension and surface cut quality were done by varying the cutting parameters of Abrasive Water Jet Machining (AWJM). Kerf dimensional deviation reducing with fly ash loading however exceeding critical loading there is a more edge damage observed. The dimensional deviation was controlled by varying the process parameters and determined the acceptance level of cutting as found by fly ash loading up to 10%. It is observed that cutting dimension deviation more when exceeding the level of 10% fly ash. Increasing jet pressure intensity reduces the fiber edge pull out and damages. Consequently, cut surface smoothness was majorly affected by fly ash loading. Surface roughness of cut surface was varied from 2 to 5µm as increasing in fly ash loading.

Inhabiting the In-Between: Childhood and Cinema in Spain's Long Transition by Sarah Thomas

Reviewed by: Inhabiting the In-Between: Childhood and Cinema in Spain's Long Transition by Sarah Thomas Elizabeth Scarlett Thomas, Sarah. Inhabiting the In-Between: Childhood and Cinema in Spain's Long Transition. U of Toronto P, 2019. 240 pp. The Spanish Transition into democracy was not only lengthy, but also plagued with contention. In fact, it has taken twice as long as the Transition itself to fathom how much went wrong with the process. Sarah Thomas discerns the presentiment of this being a fraught pathway in the films she studies in this excellent monograph. Although the adherence to representations of children in eight films of late Francoism through the democratic Transition (1970-83)—plus two others that form bookends—may seem like narrow terrain, the author connects it to a surprising number of contexts that make the whole substantially more than the sum of its parts. Meanwhile, the parts, in terms of the eight (ten, really) individual analyses, also attain an essential level of interest for scholars and students of Hispanic cinema. Other book-length studies of children in Spanish film by Sarah Wright (2013) and Erin K. Hogan (2018) with wider time frames still leave room for the concentrated and intense work with perspective, mise-en-scène, production, censorship, screening history, and reception provided by the current volume. Thomas's work is characterized by its deep analysis of film technique, close readings of [End Page 639] dialogue and plot developments (including shot-by-shot descriptions and plentiful screen shots), and a disposition toward far-reaching implications concerning historical memory far and near, recent and remote. Her gracefully shifting theoretical and critical orientation includes Philippe Ariès, Joanne Faulkner, Lisa Cartwright, Edward Soja, Britta Sjogren, Anne Higonnet, Arnold van Gennep, David Martin-Jones, D. N. Rodowick, and Kathryn Bond Stockton, as well as Gilles Deleuze, Jacques Lacan, and Julia Kristeva. Thomas builds upon scholarly treatments by previous Spanish film scholars such as Marsha Kinder and Marvin D'Lugo. All of these are referenced in the most lucid and readable manner to ground the detections of liminality that unite the figures of children and the situation of turmoil and crisis in which they were created. The introduction identifies qualities of the long democratic Transition that guided the selection of films: "[T]hese films can be seen to negotiate a series of in-betweens, in an uncanny mirroring of their socio-political context of transition, flux, potential, uncertainty, and change" (9). The children who form subjects and objects of spectatorship create a third space that reveals the impossibility of a clean break with the past, or of a linear progression into a well-defined future adult state. The child remains within the adult, to some extent unknowable and incomprehensible. The stark starting point is a brief treatment of Uruguayan director Narciso Ibáñez Serrador's cult horror flick ¿Quién puede matar a un niño? (1976), in which children exact revenge for nebulous injustices committed against them as a group. We then sidestep into Cría cuervos (1976), directed by Carlos Saura during the dictator's final months and released soon after his death. Despite the accumulation of a ponderous critical corpus around this text, Thomas's precision and sensitivity to dynamics, gaze, and filmic language yield fresh insights. The multiple planes or layers of adult narration of childhood events are joined by camera sweeps that make Ana seem to grow sideways instead of up (18). The porous boundaries between Self and Other also characterize Saura's earlier La prima Angélica (1974), in which the imbrication of temporal frames and of child and adult selves (one of many startlingly adroit analogies employed by the critic) takes the form of an adult actor (José Luis López Vázquez) stepping into the role of himself as a boy in reveries of childhood during the Civil War—Vázquez's masterful acting replicates childhood experience filtered through an adult subject frame (44). In an earlier effort of Saura's, El jardín de la delicias, a family stages scenes from the protagonist's boyhood in order to jog his memory. If they are able to make his adult self collide...

Mark Twain among the Indians and Other Indigenous Peoples by Kerry Driscoll

Reviewed by: Mark Twain among the Indians and Other Indigenous Peoples by Kerry Driscoll Joseph L. Coulombe Kerry Driscoll, Mark Twain among the Indians and Other Indigenous Peoples. Oakland: U of California P, 2018. 448 pp. Cloth, $95; paper, $34.95; e-book, $95. Kerry Driscoll’s book is a well-researched and meticulous analysis of Twain’s treatment of Indigenous peoples. It covers Twain’s early writings in Missouri and Nevada, spends considerable time on Roughing It and “The Noble Red Man,” explores his shifting positions on Natives after moving east, and ends with his commentary on Indigenous peoples in Australia and New Zealand. Describing her own book as “a work of literary archaeology” (7), Driscoll uses letters, marginalia, notebooks, laws, newspaper reports, and historical events to reconstruct helpful interpretive contexts— including the familial, literary, regional, and transnational— in order to better understand Twain’s anti-Indian biases. Driscoll rejects “the notion of a strict linear progression in the writer’s convictions; rather . . . the change was uneven, proceeding in fits and starts. Contradictions abound and are never fully reconciled” (9). Thus, while she [End Page 104] makes no radical new pronouncements about Twain’s prejudice, Driscoll uncovers reams of fascinating materials to help understand what shaped not only Mark Twain but also the American West and the United States. Driscoll is at her best when outlining historical contexts and literary connections. For example, she describes how a Missouri senator introduced a bill that “ushered in an era of ethnic cleansing so thorough that no federally recognized tribes or reservations exist within Missouri today” (16–17). The senator’s name was Thomas Hart Benton, whom, she then points out, Tom Sawyer describes as “the greatest man in the world” (16). Driscoll also connects Twain’s vitriol toward Indians to the family stories that his mother Jane Lampton Clemens shared about her experiences and those of her own mother, writing that Twain “may have inherited and uncritically accepted her bias against them” (25). In addition, Driscoll explores possible antecedents for the character “Injun Joe” and contrasts Twain’s derogatory depiction of “savages” against his propensity to “play Indian,” a tendency shared by Tom Sawyer. Readers of Western American Literature will especially appreciate chapter two, “Blind in Nevada: Early Perceptions of Indians in the West.” Driscoll uses multiple documents, including Sarah Winnemucca Hopkins’s autobiography, to recount the 1861 Pyramid Lake War, which occurred immediately before Twain arrived in Nevada, and the 1862 Owens Valley Indian War. While Twain’s letters show his awareness of these wars, the first of which was begun by white men who imprisoned and raped several Native women, Twain shows little public concern for Native peoples. Instead he focuses on the West as a “bucolic” place of “carefree comraderie” (68), which, Driscoll demonstrates, stands in stark contrast to the memories of his companion, Judge Oliver, who described their trip as filled with reminders of the recent violence. Likewise, Driscoll contrasts Twain’s attitudes about Native dispossession with those of Dan De Quille, Warren Wasson, Jacob Lockhart, Bret Harte, and his brother Orion. In subsequent chapters, Driscoll examines the context and meaning of Twain’s “The Petrified Man” hoax, the male bonding of the white miners’ club “The Pah-Utes,” and the racialized [End Page 105] and sexualized fear that informs Huck Finn and Tom Sawyer among the Indians. Driscoll deserves praise for her high level of scholarly sleuthing; she leaves few stones unturned. That said, she also creates inconsistencies that are hard to ignore. For example, after informing readers that the term “Digger” is a racial epithet “invented by Anglo-Saxon settlers,” which is “in many ways comparable to nigger” (110), she uses the term in the same chapter, repeatedly referencing “the Digger tribes of the Great Basin” (118). She also struggles with a dilemma faced by many scholars: how to characterize an admired author who also advocates abhorrent policies, such as exterminating Natives. While Driscoll exposes Twain’s racism— asserting that “he never succeeded in fully exorcising this racial animus” (13)— she also defends “our nation’s greatest storyteller” against charges that he’s an “absolute Indian hater” because he wrote a letter against a bounty...

Understanding Dynamics of Success at Midcareer Stage of Management Employees

Mid-career stage is also called as midlife, mid-career life mid work life. There is a linear progression in one’s life and an individual moves up in the career ladder through changing various jobs and being ready to hop further. In the process there are many factors which lead to success of an individual .As the journey moves on the factors varies from one to another. Competition is rising gradually in all sectors and so do education sector is also affected. This picture is clearly visible in management institutes or b schools which are mushrooming every nook and corner. These institutions are attracting students mostly through branding to get more and more admission and enrolment into their institute. This is a theoretical study and an attempt to analyze the branding of management institute and other factors influencing the success of midlife career stage into the professional life. Both secondary and primary data was studied on the given topic Primary data was collected by survey of 360 management employees (age group 35-45 years) who have done MBA from different branded Management education Institutions. A well-structured questionnaire with closed ended questions to know the effect of branding and other influencers on the success in their latter part of career was analyzed. The technique used is multiple linear regression techniques. Reputation, Image, Ranking, Accreditation, foreign collaboration and industry linkages has significant impact on to the initial part of students joining the companies which affects a prospective candidate during the placement but gradually as he moves upward in the ladder of his career the other factors like type of personality he develops, past experiences in different companies, network and relationships with high potentials and capable people start influencing more to his success. Few limitations came across like study was conducted in the city of Mumbai hence geographically limited to one cultural and social region of Maharashtra. The managerial implications is that this study will be helpful to the management institute to find the correlation between the branding strategy and other success factors at mid-career success based on which they may prepare their future marketing strategies. The originality of the study is to connect branding and other factors influencing mid-career success.

Othello in Harlem: Transforming Theater in Djanet Sears's Harlem Duet

Djanet Sears's Harlem Duet reimagines Shakespeare's Othello by weaving together three stories about Othello and his first wife, Billie, across three distinct time periods: the Civil War era, the Harlem Renaissance, and the present day. This essay centers on the scenes set in the Harlem Renaissance, a timeline that appears to unfold out of chronological order. By disrupting the linear progression of time, Sears transforms the theater into a platform that amplifies the stories of the oppressed through the dramatization of the ongoing, persistent cycle of oppression.

The Regulator Regulated: A Genealogy of the Pakistani Broadcast Media and its State of ‘Double Capture’ in the Post-Musharraf Era

This article traces a genealogy of regulatory and other tactics through which the Pakistani broadcast media is controlled, comparing the colonial context of the development of these tactics with the postcolonial circumstances of their re-deployment. Archival research into the East India Company’s documents from the turn of the nineteenth century uncovers the development of regulatory regimes referred to as Censorship, Self-Regulation, and Licensing, in addition to extra-legal techniques. The article argues that colonial tactics still form key components of Pakistan’s postcolonial broadcast regulations. However, in the past, one regime was replaced by another in a linear progression; today these regulatory techniques appear concomitantly stacked, selectively deployable and enfolded within an expanding array of extralegal techniques. The article seeks to move beyond conceptions of ‘regulatory capture’ or ‘media capture’ by applying the Deleuzian concept of ‘double capture’: in the case of the Pakistani broadcast media, the government regulator (and to some extent the government itself) is captured by ‘media power’ in the same instance that the media assemblage itself becomes subject to ‘state capture’ through extralegal means. Part one focuses on the decades when the colonial state first regulated newsprint (1780–1823), tracing the development from extralegal controls to a succession of legal regulations through which Company administrators could regulate – rather than be regulated by – colonial newsprint. Part two considers the paradoxical situation in Pakistan’s contemporary broadcast regulations (2002–2018), where PEMRA seems powerless to regulate the media, yet the media is subject to a ‘double capture’ through a combination of legal and extralegal modes of control.

Thematic Progression in Online Algerian Newspaper Articles: Insights to Producing Coherent Texts

This paper presents an analysis of the preferred thematic progression patterns used in a sample of online English versions of Algerian news articles written by Algerian journalists and appearing originally in Arabic. The purpose is to detect the recurrent patterns in this media genre. Departing from the more clause-centered models for the analysis of thematic development, the present study uses a categorization of thematic progression patterns derived from McCabe’s (1999) and Daneš’s (1974) models as a framework for the analysis. The corpus of the study comprises 30 online English articles that appeared in two Algerian newspapers Echorouk and Ennahar. The analysis proceeded by a T-unit segmentation of the collected articles in terms of themes and rhemes. Subsequently, determining intersentential connections as to the reiteration, alteration, or splitting of these two central constituents followed. Ultimately, patterns of sequencing were defined in the entirety of texts in the corpus. The results point toward a more frequent use of Simple Linear Progression and Constant Theme Progression. Derived Theme and Split Theme patterns are rarely used, while Split Rheme Progression does not feature in the data. Significant rates of ruptured themes are also recorded. The paper concludes by deriving useful insights as to finding ways of upgrading the writing of more coherent newspaper articles based on careful consideration of thematic progression.

CAREER PLATEAUING AND IT’S RELATIONSHIP WITH SECONDARY SCHOOL TEACHERS’ PURSUIT OF POST-GRADUATE STUDIES IN NYANDARUA AND MURANG’A COUNTIES, KENYA

Purpose: Teachers in Kenya exhibit signs of career plateauing, and are registering for post-graduate courses in large numbers. This study investigated whether teachers’ pursuit of post-graduate studies is a result of career plateauing. The purpose of the study was to determine the relationship between career plateauing and secondary school teachers’ pursuit of post-graduate studies in Nyandarua and Murang’a counties, Kenya. The objectives of the study were to: determine types and levels of career plateauing experienced by secondary school teachers of public schools in Nyandarua and Murang’a Counties; determine the relationship between career plateauing and teachers’ decisions to pursue various Post-Graduate courses; and find out whether the structural or job content type of career plateau predicts teachers’ decisions to pursue various Post-Graduate courses among secondary schools teachers in public schools in Kenya.Methodology: The study employed the correlational research design. The target population of the study comprised of all the 5,022 teachers (3,581 in Murang’a County and 1,441 in Nyandarua County) in all the public schools in Nyandarua and Murang’a Counties except those which were used in the pilot. From this population, the sample size for each county was computed using the sample size computation formula by Krejcie & Morgan (Cohen, Manion & and Morrison, 2007), which gave 304 teachers from Nyandarua County and 348 teachers in Murang’a County. Stratified random sampling was used to select 304 teachers from Nyandarua County and 348 teachers from Murang’a County giving a total of 652 teachers. In Nyandarua County, the sample size was 152 male and 152 female teachers, while in Murang’a County there was 174 male and 174 female teachers. A questionnaire designed for teachers was used as the main tool for data collection. The study generated quantitative data, which was analyzed using descriptive and inferential statistics. Qualitative data was reported according to themes and involved the use of frequencies and percentages. Linear progression and Analysis of Variance were also used.Results: Decisions to pursue post-graduate studies is expected to increase 0.014 when structural plateauing rises by one and decrease by 0.012 when job content plateauing goes up by one. Both structural and job content plateauing were found to predict decisions to pursue post-graduate studies significantly at p<0.05.Contributions to theory, policy and practice: The Teachers Service Commission should develop a clear road map for career advancement of the teachers to reduce career plateauing. The Teachers Service Commission in collaboration with the ministry of education should design a skills upgrade for teachers through capacity development programmes which should be a requirement for those joining the profession and which should form a basis for promotion

Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: A systematic review and meta-analysis.

Colorectal cancer (CRC) exhibits a linear progression from normal colonic epithelium, adenoma initiation, carcinoma transformation and even to metastasis. Diet changes might influence carcinogenesis and prognosis. We aimed to determine the effects of vitamin D and calcium on colorectal adenoma incidence, malignancy development and prognosis. Systematic literature searches (PubMed, Embase, and Cochrane Library databases) and hand searches were performed by September 30, 2019. A random-effects model was adopted to pool relative ratios (RRs) for colorectal tumour incidence or hazard ratios (HRs) for CRC mortality. Stratified analyses were performed by gender, tumour location, calcium intake level and ethnic group. Total 854,195 cases from 166 studies were included. The colorectal adenoma incidence was inversely correlated with the circulating 25-hydroxyvitamin D [25(OH)D] level (RR: 0.80, 95% CI: 0.71-0.89), vitamin D intake (RR: 0.87, 95% CI: 0.82-0.92) and calcium intake (RR: 0.86, 95% CI: 0.81-0.91). The CRC incidence was decreased by circulating 25(OH)D (RR: 0.67, 95% CI: 0.59-0.77), vitamin D intake (RR: 0.85, 95% CI: 0.78-0.93) and calcium intake (RR: 0.75, 95% CI: 0.70-0.79). High-level circulating 25(OH)D triggered better overall survival (HR: 0.67, 95% CI: 0.57-0.79) and CRC-specific survival (HR: 0.63, 95% CI: 0.53-0.74). Stratified analyses showed that vitamin D and calcium significantly suppressed colorectal tumour incidence among women. Left-sided CRC risk was reversely related to circulating 25(OH)D (RR: 0.60, 95% CI: 0.41-0.88) and vitamin D intake (RR: 0.73, 95% CI: 0.57-0.93). Circulating 25(OH)D decreased colorectal adenoma (RR: 0.63, 95% CI: 0.48-0.82) and CRC (RR: 0.69, 95% CI: 0.56-0.86) risk in populations with higher calcium intake. European and American populations benefited more from vitamin D intake against colorectal tumour. A significant dose-response relationship was observed between intake of vitamin D or calcium and colorectal tumour incidence. Vitamin D and calcium play additively chemopreventive roles in colorectal adenoma incidence, malignant transformation and progression, especially for women and left-sided CRC patients.

Migration routes and habitat use of a highly adaptable salmonid (sea trout, Salmo trutta) in a complex marine area

BackgroundUnderstanding fish movements and migrations are paramount for management and conservation efforts. By applying Hidden Markov Models (HMMs) on records from electronic tags, migration routes of tagged fish can be reconstructed and new insights to the movement ecology of a species can be gained. We demonstrate the usability of HMMs on a widespread, iteroparous salmonid (sea trout, Salmo trutta) in a complex marine area with highly variable temperatures and salinities within small geographic distances. Understanding how the highly adaptable sea trout cope with these complex conditions could shed new light on factors driving the movement ecology of salmonids. Migration tracks of fish migrating at sea are reconstructed by applying an HMM on temperature and depth records from eight wild post-spawned sea trout from four Danish rivers.ResultsThe fish migrated at sea for 47–142 days. Estimated positions of all fish were close to the coast (< 100 km) throughout the marine period, but migrations along coastlines up to 580 km away from the natal river occurred. Seven of eight individuals resided in or actively migrated into stratified or shallow marine areas that heat up fast during spring, while all eight individuals resided in deeper and more heterogeneous areas that heat up slow during summer. All fish entered the Skagerrak (located between Denmark and Norway) at some stage during summer. Migrations were directed into less saline areas during the first 15 days at sea for all individuals. Mean linear progression of the fish was 16 km day−1 (range 0–58 km day−1).ConclusionsThe results corroborate the expectation that sea trout are more coastally orientated than other salmonids, but also suggest that longer migrations occur in the seas surrounding Denmark compared to elsewhere. This could be a consequence of the fish seeking out habitats with optimal conditions (e.g. salinity, temperature, predation and foraging options) for growth in different parts of the year. The coinciding movement from shallow or stratified marine areas that heat up fast during spring to deeper, more well-mixed areas that heat up slow during summer suggested that some habitat selection had occurred. These results shed new light on factors influencing marine migrations in salmonids and demonstrate how HMMs can expand our knowledge on behaviour and movement ecology of marine fishes.

Conventional Chemotherapy Treatment Induces Unique Patterns of Clonal Evolution in a North American Adult T Cell Leukemia/Lymphoma Cohort

Adult T cell leukemia / lymphoma is a rare neoplasm with dismal cure rates and poor response to chemotherapy. The genetic basis of refractoriness against conventional agents is not known. We follow one of the largest cohorts of ATLL in the US and recently showed that North American ATLL (NA-ATLL) has a distinct mutational profile from Japanese ATLL (J-ATLL) with a higher incidence of epigenetic mutations (Shah et al, Blood, 2018; 132(14):1507-1518). Here, we analyze the mutational landscape of ATLL clones at diagnosis and at relapse in a pilot study of 7 NA-ATLL patients using deep targeted sequencing of 236 recurrently mutated genes. Our goal was to examine clonal evolution patterns that may result as a consequence of the selective pressure of chemotherapy by determining changes in mutational profiles as well as clonal abundance on patients with aggressive ATLL [acute and lymphomatous] (Table 1). All patients were treated with EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide and Doxorubicin) chemotherapy after initial diagnosis except one patient who received interferon therapy. Distinct patterns of clonal evolution were observed in patients with primary refractory disease when compared to those who relapsed after an initial remission. Group 1 has 3 cases (Pts 1 to 3), all of which experienced early relapse and showed mutation patterns suggestive of clonal replacement by a new emerging clone at relapse. Group 2 has 3 patients (Pts 4-6) that are characterized by worsening of primary refractory disease. Mutation patterns in the before-and-after sample pairs suggest linear progression from a previously existing clone during therapy. The clonal evolution status was not resolved in our third group (Pt#7) indicating that mutations outside the 236 genes evaluated might have been present. Frequent epigenetic mutations were found in both diagnostic and refractory/relapsed samples. Surprisingly, 4 epigenetic mutations (KMT2D, EP300, SPEN, SETBP1) identified in 4 cases were confirmed or suspected of germline origin. This suggests that ancestral genomic differences between the Caribbean and Japanese populations could contribute to the mutational and clinical disparities between NA- and J-ATLL. Multiple mutations with similar variant allele frequencies (VAF) at the time of relapse were identified, suggesting simultaneous acquisition of several mutations during clonal evolution. Clonal replacement by an emerging clone (Group 1) such as GATA3 (Pt#3) or KMT2D (Pt#1) (either germline or founding mutation) was observed in patients who achieved an initial response. On the other hand, in primary refractory disease (Group 2), relapse was driven by dominant TBL1XR1 mutations in 2 out of the 3 cases either alone (Pt#6) or in combination with mutated SMARCB1 (Pt#5). The protein encoded by TBL1XR1 is a negative regulator of the nuclear receptor corepressor (NCoR) /histone deacetylase 3 (HDAC3) complex. Therefore, TBL1XR1 inactivation is expected to result in hyper-activity of NCoR/HDAC3, an epigenetic abnormality targetable by HDAC inhibitors. SMARCB1 is also an epigenetic regulator associated with several malignancies and has been targeted with alisertib. A subclonal expansion of EP300 (a histone acetyltransferase) appears to drive relapse in the other case of this group (Pt#4). Therefore, our primary refractory cases show that epigenetic mutations seem to be of utmost importance not only at diagnosis as we have previously shown, but as the driving force behind chemotherapy refractoriness and subsequent relapse. Conclusion: To our knowledge, this is the first mutation-based clonal evolution study aimed to examine dynamic changes induced by chemotherapy among NA-ATLL patients. Early relapse appears to be driven by the emergence of new mutant clones. On the other hand, primary refractory disease appears to have epigenetic drivers that convey chemotherapy refractoriness and evolve from linear progression of a previously existing clone. Serial mutational testing can provide critical information on clonal architecture and identify actionable molecular vulnerabilities in a cohort without effective therapeutic options and a dismal prognosis. Disclosures Sica: Physician's Education Resource (PER): Honoraria. Shah:Physicians' Education Resource: Honoraria. Steidl:Aileron Therapeutics: Consultancy, Research Funding; Stelexis Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Scientific Co-Founder; Pieries Pharmaceuticals: Consultancy; BayerHealthcare: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Consultancy. Verma:Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding.

Clinical Evidence Against the Continuum of Low-Primed Uncommitted Hematopoietic and Progenitor Cells (CLOUD-HSPC) Concept for Hematopoiesis

Introduction: The classical model of blood stem cell differentiation is branch-like linear HSPC progression from progenitor multi/oligo potent stem cells to differentiated mature cell types. An alternative model, referred to as CLOUD-HSPC, proposes bone marrow (BM) HSPCs continuous and direct differentiation into unipotent cells of myeloid lineage (neutrophils (N), basophils (B), eosinophils (E), monocytes (M), mast cells, megakaryocytes (platelets) and erythrocytes without linear stem cell commitment (Velten Nat Cell Biol 2017). Pegfilgrastim (Peg), and the non-colony stimulating agent Plinabulin (Plin) prevent chemotherapy (chemo) induced neutropenia (CIN) in cancer patients (pts), and both exert BM effects leading to CD34+ cell mobilization (Blayney ASH 2017, 2018). In mice, Plin enhances LSK (Lin-Sca+cKit3+) cell differentiation in BM (Ghosh, AACR 2018). Here we clinically validated the CLOUD-HSPC concept by analyzing peripheral blood mononuclear cell (PBMC) counts derived from two bifurcating progenitor cells 1. Granulocyte-Monocyte Progenitor (GMP) producing N,M,E and B and 2. Common Lymphoid Progenitor (CLP) producing lymphocytes (L), after exposure to Peg or Plin in a CIN setting. With linear stem cell commitment, increase in the differentiated mature cell counts would positively inter-correlate, and with CLOUD-HSPC, they would not. Methods: In the Phase 3 portion of study BPI-2358-105 (NCT03102606), pts with NSCLC, BC or HRPC received pre-medication with dexamethasone (Dex) on day (D) -1,0, and 1 and docetaxel (Doc) on day (D) 1. Pts were randomized 1:1 to either Plin 40 mg (n=52), given 30 min after Doc infusion D1, or Peg 6 mg (n=53), D2. Central laboratory (Covance Laboratory) PBMC counts were obtained at screening, D 1,2, 6,7,8,9,10, 15 in Cycle 1, and correlated with each other at a pre-planned interim analysis. D1 and D2 data points were omitted due to confounding effects of Dex and demargination. Data of Plin and Peg were combined, since both drugs exert BM effects leading to increased N cell counts and showed similar correlation trends. Results: Maximum increases in % from screening value on D5-D15 of each N,M,E,B and L counts correlated with each other. Pearson correlation coefficients (r) after linear regression and corresponding p-value are summarized below. Conclusions: There is a linear and positive inter-correlation between differentiated mature cells derived from the GMP and CLP lineage, proving strong clinical evidence against CLOUD-HSPC, but in favor of the classical linear commitment model. Table Disclosures Mohanlal: BeyondSpring Pharmaceuticals: Employment. Blayney:BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment.

TMOD-24. DEVELOPMENT OF A NOVEL IN VIVO MODEL OF LUNG-TO-BRAIN METASTASIS PROGRESSION

Abstract Brain metastases (BM) are the most common neoplasm to affect the adult central nervous system, occurring ten times more frequently than primary brain tumor. BM develop in 40–50% of advanced lung adenocarcinoma (LUAD), and the lack of durable response to chemotherapy, immunotherapy, or targeted therapy will result in death within a year of BM diagnosis. Despite the high burden of disease, dismal prognosis, and the increase in incidence over time, the biological underpinnings of BM remain poorly understood due to both the difficulty of obtaining a sizable collection of metastatic tissue samples as well as a lack of clinically relevant models. As such, it is possible that the inability to properly study this disease may result in metastasis driver-genes remaining undiscovered. Typical models of BM utilize direct implantation of tumor cells into the mouse brain, or inoculation into the blood via intracardiac/intracarotid injections; these routes are invasive and cannot fully recapitulate the entirety of the metastatic cascade. Here we present a novel, non-invasive method to develop primary lung tumors and brain metastases. A 10µL tumor cell suspension in phosphate-buffered saline was applied to the nostrils of lightly anesthetized mice, allowing direct deposit of cells into the lungs. Mice were monitored with bioluminescence imaging bi-weekly and culled at 2.5–3 months post-inoculation. Lungs and brains were also removed and imaged, where tumors in both organs were observed. Further research is necessary to elucidate either the linear or parallel progression of tumor formation within this model. Nonetheless, our technique presents a novel preclinical tool to interrogate the metastatic process, allowing validation of genetic drivers as well as therapeutic screening.

Uncovering the subtype-specific temporal order of cancer pathway dysregulation.

Cancer is driven by genetic mutations that dysregulate pathways important for proper cell function. Therefore, discovering these cancer pathways and their dysregulation order is key to understanding and treating cancer. However, the heterogeneity of mutations between different individuals makes this challenging and requires that cancer progression is studied in a subtype-specific way. To address this challenge, we provide a mathematical model, called Subtype-specific Pathway Linear Progression Model (SPM), that simultaneously captures cancer subtypes and pathways and order of dysregulation of the pathways within each subtype. Experiments with synthetic data indicate the robustness of SPM to problem specifics including noise compared to an existing method. Moreover, experimental results on glioblastoma multiforme and colorectal adenocarcinoma show the consistency of SPM's results with the existing knowledge and its superiority to an existing method in certain cases. The implementation of our method is available at https://github.com/Dalton386/SPM.

Simplifying Age Progressions within the Cook‐Austral Islands using ARGUS‐VI High‐Resolution 40Ar/39Ar Incremental Heating Ages

AbstractThe Cook‐Austral islands do not exhibit a simple linear age progression from a single point of active volcanism, in contrast to other Pacific island chains. Explaining this anomaly, however, has been difficult due to the low reliability of the existing K/Ar ages for these islands. Here we present 56 new incremental heating 40Ar/39Ar age determinations for eight of the Cook‐Austral islands. We show that these 40Ar/39Ar ages are on average 10–40% different and generally older than the K/Ar ages for the same samples, are more reproducible within single lava flows, exhibit less scatter among data from a single island, and are more reliable than published K/Ar age determinations. Our new data result in two clearly defined and matching age‐progressive trends, with origins at the Macdonald and Arago seamounts. This supports the hypothesis that the Macdonald and Rurutu tracks formed by two contemporaneous hotspots aligned in the direction of plate motion. Compared to other volcanic chains on the Pacific plate, the Cook‐Austral hotspot tracks record angular rotational plate velocities (0.96 ± 0.05 to 1.09 ± 0.04°/Ma) similar to Hawaii (1.15°/Ma) but faster than Samoa (0.63°/Ma). This may imply that hot spot location relative to tectonic boundaries may have an effect on the age progressions recorded by volcanic chains. Specifically, the Cook‐Austral and Hawaii hot spots have over the last 30 Myr been located truly intraplate and thus far away from any tectonic boundary, while Samoa has been proximal to the active Tonga‐Kermedec subduction zone.

Competency-based education in transitioning nurse practitioner students from education into practice.

Competency-based education (CBE) provides a framework for nursing programs including those educating nurse practitioners (NPs). The basic assumption of CBE is that the student will demonstrate acquisition of the identified essential knowledge, skills, and attitudes expected for the designated educational process before leaving the learning environment. The work done to date in developing competencies and progression indicators provides the critical basis to move toward a common language and clear expectations for the continuum of linear progression of proficiency. Entrustable professional activities (EPAs) are built on competencies and stated as measurable activities that providers can be expected to do, at varying levels of competence or trust or supervision, and allow the faculty member, preceptor, or supervisor to make decisions as to what teaching methods and level of supervision are needed. Numerous methods are used to measure competency in clinical skill knowledge, performance, and practice readiness including clinical preceptor feedback, objective structured clinical examination, and simulation, just to name a few. NP programs continue to struggle with the education practice gap between theory and the actual provision of care. The discussion about novel and reliable methods for measurement of competencies must address the strategic importance of a consensus about when, where, and how students can obtain the appropriate amount and type of experience and supervision required in the transition to independent practice. There is also a significant need for processes and standardized guidelines that can contribute to EPA development.

Mark Twain among the Indians and Other Indigenous Peoples

Mark Twain among the Indians and Other Indigenous Peoples

Extended Printmaking: (Im)Pure Print practices | Gravura prolongada: Práticas impuras

This article seeks to reveal how the Pure Print International Printmaking Meeting may contribute with new insights towards the current quest for a relevant printmaking practice. The meeting was converted into a research platform, allowing a compilation and experiment with our desire for a full printmaking experience. Refusing a linear technological progression and rigid research plans, we moved into an impure practice seen as a transition into an intermedia experience. Slowly, we embarked on a series of experiments to pursueprocesses that have the potential of a photographic reproduction and looked back at a past where terms as “chemical printing” referred to the print capacity to literally transfer a drawing as first found in stone lithography. In the end, multiple technological incursions and cross academic contributions confirmed how printing research may be used to make the production of contemporary artistic printing practices easier and expand their aesthetic possibilities. Moreover, the modes of production employed reinforce perceptionsof how context, conditions, and processes must be set up for a creative, resolutive, and innovative research to take place. By emphasizing the use of local resources, aligning craft and practice, and selecting connections between printmaking and creative practices at large, we shed new light on how printmakers may construct knowledge.

Wound healing efficacy of Jamun honey in diabetic mice model through reepithelialization, collagen deposition and angiogenesis

Diabetic patients are frequently afflicted with impaired wound healing where linear progression of molecular and cellular events compromised. Despite of meaningful progress in diabetic treatment, management of diabetic chronic wounds is still challenging. Jamun (Syzygium cumini) honey may be a promising candidate for diabetic wound healing and need to explore in detail.So present study was designed to evaluate the efficacy of Jamun honey (JH) for diabetic wound healing in in vitro wound (primary fibroblasts) model and in in vivo of diabetic mice (Streptozotocin induced) model. The fibroblast cell model was studied for migratory behaviour and myofibrolasts infiltration under honey interventions via scratch/migration assay, immuno-cytochemistry and western blot. We applied FDA approved Manuka honey (MH) as positive control and JH as test honey to evaluate wound re-epithelialization, sub-epithelial connective tissue modification and angiogenesis via histo-pathological and immuno-histochemical analysis. JH (0.1% v/v) dilution has notably improved wound closure, migration with concomitant α-SMA expressions in vitro. Topical application of JH in diabetic mice model showed significant (*p ≤ 0.05) wound closure, reepithelialization, collagen deposition (I/III) and balanced the myofibroblasts formation. It also modulated vital angiogenic markers (viz HIF-1α, VEGF, VEGF R–II) significantly (*p ≤ 0.05). All these observations depicted that JH promotes sequential stages of wound healing in diabetic mice model. The results of the present study established Jamun honey as good as Manuka honey considering wound closure, re-epithelialization, collagen deposition and pro-angiogenic potential.