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Purpose To determine the effectiveness of pharmacy consultation in managing epoetin alfa-epbx dosing for inpatients on hemodialysis. Methods This multisite, retrospective cohort study evaluated the implementation of an initial dose consultation for epoetin alfa-epbx by pharmacists. A pre-post cohort study evaluated patients from August 2020 through January 2021 and August 2021 through January 2022, respectively. Hospitalized patients were included if they were at least 18 years of age, received hemodialysis, and were administered an erythropoiesis-stimulating agent (ESA) for anemia due to chronic kidney disease. Patients were excluded for religious objections to receiving blood products or if patients were discharged or died before their first hemodialysis session. The primary outcome was the average epoetin alfa-epbx acquisition cost per patient. Secondary endpoints were the epoetin alfa-epbx overall pharmacy purchasing cost, the average dose, and the number of administered doses. A subgroup analysis was performed for patients in the post group with an outpatient ESA before admission to determine the epoetin alfa-epbx days saved. Results A total of 264 patients were included in the pre group, and 272 patients were included in the post group. The average acquisition cost was significantly lower in the post group ($1,681.77 vs $1,041.35, P < 0.0001). The overall pharmacy purchasing cost was also lower in the post group ($148,970.89 vs $127,873.25). The post group had a significantly lower average dose (13,694 vs 10,112 units, P = 0.0004), while the number of administered doses did not differ significantly between the groups (2.09 vs 1.79 doses, P = 0.0668). The subgroup analysis included 83 patients, which yielded 53 epoetin alfa-epbx days saved. Conclusion Pharmacist-driven ESA dosing was associated with significant decreases in ESA average acquisition cost and average total dose per patient.

Purpose:In addition to opioid abuse and dependency, opioid use can lead to opioid related adverse drug events (ORADEs). ORADEs are associated with increased length of stay, cost of care, 30-day readmission rate, and inpatient mortality. The addition of scheduled non-opioid analgesic medications has shown to be effective in reducing opioid utilization in post-surgical and trauma populations, but evidence in entire hospital patient populations is limited. The objective of this study was to determine the effects of a multimodal analgesia order set on opioid utilization and adverse drug events in adult hospitalized patients. Methods: This retrospective pre/post implementation analysis was conducted at 3 community hospitals and a level II trauma center between January 2016 and December 2019. Patients included were 18 years of age or older, admitted for greater than 24 hours, and had at least one opioid ordered during hospital admission. The primary outcome of this analysis was the average oral morphine milligram equivalents (MME) used on days 1 through 5 of hospitalization. Secondary outcomes included the percentage of hospitalized patients with an opioid ordered for analgesia who received a scheduled non-opioid analgesic medication, the average number of ORADEs recorded in nursing assessments on hospitalization days 1 through 5, length of stay, and mortality. Multimodal analgesic medications included acetaminophen, gabapentinoids, non-steroidal anti-inflammatory drugs, muscle relaxants, and transdermal lidocaine. Results: The pre- and post-groups included 86 535 patients and 85 194 patients, respectively. The average oral MMEs used on days 1 through 5 were lower in the post-group ( P

A competing stimulus assessment (CSA) is commonly used to identify leisure items for use in treatments designed to decrease automatically reinforced problem behavior. However, this type of assessment may not yield useful information if participants do not readily engage with leisure items. The purpose of this study was to evaluate a modified CSA that included additional treatment components (i.e., prompting, prompting plus differential reinforcement of alternative behavior). The modified CSA identified the treatment components and leisure items that were most effective for increasing leisure-item engagement and decreasing problem behavior for each participant. Modified CSA outcomes maintained during an extended treatment analysis in a natural setting and when intervention components were faded.

The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed “minimal residual disease”. The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, BCR-ABL-independent mechanisms exist which sustain the survival of leukemic stem cells (LSCs). Although other markers of a primitive CML LSC population have been identified in the preclinical setting, only CD26 appears to offer clinical utility. Here we demonstrate consistent and selective expression of CD93 on a lin−CD34+CD38−CD90+ CML LSC population and show in vitro and in vivo data to suggest increased stem cell characteristics, as well as robust engraftment in patient-derived xenograft models in comparison with a CD93− CML stem/progenitor cell population, which fails to engraft. Through bulk and single-cell analyses of selected stem cell and cell survival-specific genes, we confirmed the quiescent character and demonstrate their persistence in a population of CML patient samples who demonstrate molecular relapse on TKI withdrawal. Taken together, our results identify that CD93 is consistently and selectively expressed on a lin−CD34+CD38−CD90+ CML LSC population with stem cell characteristics and may be an important indicator in determining poor TKI responders.

Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients.

International audience; The open access (OA) article processing charges (APC) project is a longitudinal study of the minority of fully OA journals (27% in 2016) that have APCs. The global average APC shows little change; in USD, 906 in 2010, 964 in 2016, 974 in 2017. The average masks currency differences and the impact of a growing market; new APC journals often start with an APC of 0. Traditional commercial scholarly publishers are entering the OA market: the largest OA journal publishers’ portfolios in 2017 were Springer, De Gruyter, Elsevier, and Wolters Kluwer Medknow. However, these are a small portion of OA journal publishing which is still marked by a very long tail and extensive involvement by very small, often university or society publishers. APC pricing shows a wide range and variability. The APC market can be described as volatile.

Author(s): Morrison, Heather; Valachovic, Yana; Nunamaker, Claralynn | Abstract: Part 19 of the 24-part Forest Stewardship Series. The Forest Stewardship Series is a 24-part free online publication that provides owners of California forestland with a comprehensive source of information pertinent to the management and enjoyment of their lands. This information will help you formulate and implement strategies for achieving your personal goals as a landowner. The series provides an introduction to the lifelong study of forest stewardship that is part of owning forest property.

Joseph Richter, a prolific writer of the Viennese Enlightenment, published a satirical dictionary in 1782 called theABC Book for Big Children. Here, under the heading “men of letters” (Gelehrte), he wrote, “Emperor Augustus brought them to his table. Among the great nobility of our time, they eat out on the steps.” This criticism of insufficient patronage, marginalization, and loss of status seemed to come at an odd time. By 1781, the current Emperor and Habsburg monarch, Joseph II, freed censorship to the extent that Richter's satire could be published; writers sought to live from their works; and Vienna sustained a vibrant intellectual scene among the booksellers, coffee shops, and Freemason lodges. Yet Richter's lamentation reveals a complex reaction to the transition to a more modern, participatory, and even democratic knowledge culture.

Patients with heart failure (HF) who have been discharged from a home care agency are a particularly vulnerable group at risk for poor outcomes and high rehositalization rates. The primary aim of this experimental study was to determine the efficacy of a telemonitoring and self-care education intervention in reducing hospitalization and improving quality of life and patient’s knowledge of HF after home care discharge. Ninety-three participants completed the study. The primary outcome of 90-day post–home care discharge hospitalization was significantly reduced in the intervention group compared to controls (9 vs. 18, p - .046). HF knowledge ( p = .013) and QOL ( p = .004) were significantly increased in intervention group patients in comparison to control group patients’ at the study endpoint.

Chronic myeloid leukemia (CML) is an excellent model of the multistep processes in cancer. Initiating BCR-ABL mutations are required for the initial phase of the disease (chronic phase, CP-CML). Some CP-CML patients acquire additional mutation(s) that transforms CP-CML to poor prognosis, hard to treat, acute myeloid or lymphoid leukemia or blast phase CML (BP-CML). It is unclear where in the hemopoietic hierarchy additional mutations are acquired in BP-CML, how the hemopoietic hierarchy is altered as a consequence, and the cellular identity of the resulting leukemia-propagating stem cell (LSC) populations. Here, we show that myeloid BP-CML is associated with expanded populations that have the immunophenotype of normal progenitor populations that vary between patients. Serial transplantation in immunodeficient mice demonstrated functional LSCs reside in multiple populations with the immunophenotype of normal progenitor as well as stem cells. Multicolor fluorescence in situ hybridization detected serial acquisition of cytogenetic abnormalities of chromosome 17, associated with transformation to BP-CML, that is detected with equal frequency in all functional LSC compartments. New effective myeloid BP-CML therapies will likely have to target all these LSC populations.

Sustaining the Knowledge Commons, funded throughSSHRC's Insight Development Program aims totransition scholarly publishing from subscriptions /purchase to open access. This presentation focuseson a correlational study of DOAJ journals, exploringrelationships between tendency to charge articleprocessing charges, subjects and number of articles.Le Soutien au patrimoine de connaissances, financépar le Programme de développement Savoir du CRSHvise à faire passer l’édition savante du mode parabonnement ou par achat au mode libre accès. Cetteprésentation se concentre sur une étude decorrélation de revues disponibles en libre accès(DOAJ), en explorant les relations entre la tendance àfacturer des frais de traitement pour un article, lessujets et le nombre d’articles.

Abstract 290 Multiplex Ligation-dependent Probe Amplification (MLPA) provides an accurate and reliable high throughput method to screen for copy number abnormalities (CNA) of the significant genes in BCP-ALL. We have screened a consecutive cohort of 1427 childhood BCP-ALL patients treated on UKALL97 and UKALL2003 using the P335 SALSA MLPA kit IKZF1 (MRC Holland, The Netherlands). We here report the association of CNA involving these genes with clinical features. The overall breakdown of CNA was CDKN2A/B 28% (395), ETV6 22% (312), PAX5 19% (272), IKZF1 14% (196), RB1 6% (92), BTG1 6% (89) and EBF1 2% (30), as well as the rearrangement, P2RY8-CRLF2 4% (63). The cohort comprised 762 (54%) males and 665 (46%) females. There was no shift in the gender balance according to CNA. The median age of the entire cohort was 5 years (range 1–23) with 24% of patients being ≥10 years. There was some correlation between the distribution of CNA and patient age. Patients with IKZF1 and CDKN2A/B deletions were significantly older at 7 years (p50×109/L (each p There is particular interest in IKZF1 and CRLF2 in relation to outcome in BCP-ALL. We have previously shown an intermediate outcome for patients with CRLF2 rearrangements. We here examined the prognostic effect of IKZF1 deletions in this patient cohort; but excluded Down syndrome and BCR-ABL1 positive patients from survival analyses. Among 469 ALL97 patients, 13% (63) had IKZF1 deletions and after a median follow-up time of 9.5 years, 49% (31) had relapsed and 40% (25) had died. In the NCI standard risk (SR) group, patients with IKZF1 deletions had a significantly inferior event free survival (EFS) at 5 years (61% v 85%, p=0.0006). However, the effect appeared to be largely confined to patients with intermediate risk cytogenetics (63% v 85%, p=0.025) rather than those with good risk cytogenetics (75% v 87%, p=0.2915). As expected the NCI high risk (HR) patients with IKZF1 deletions had an inferior EFS: 50% v 68%, p=0.0112. In ALL2003, 776 patients with a median follow-up time of 3.9 years were available for analysis. Among 11% (87) patients with IKZF1 deletions, 13% (11) had relapsed and 5% (4) died in remission, resulting in a significantly inferior 5 year EFS: 78% v 90% p=0.0025. Of note, 8/11 IKZF1 deleted patients who relapsed were MRD positive (>0.01%) at day 28 and only 1/22 patients with good risk cytogenetics and IKZF1 deletion relapsed. There was no evidence that the type of deletion (deletion of exons 4–7 vs others) was linked to outcome in either the ALL97 or ALL2003 cohort. In conclusion, we have shown that IKZF1, PAX5 and/or CDKN2A/B aberrations are significantly associated with NCI HR, which may point to an associated poor outcome. Indeed, we showed that patients with IKZF1 deletions had an inferior outcome overall. However, there was evidence to suggest that the effect was pleiotropic and, importantly, IKZF1 deleted patients treated on ALL2003 in general achieved a respectable EFS rate of 75% at 5 years. Although in most studies IKZF1 deletions have been associated with a poor prognosis in BCP-ALL, while the risk relating to CRLF2 has been variable, thus far these findings, including those from this study, do not support changes to treatment for patients with these abnormalities. Disclosures: No relevant conflicts of interest to declare.

This article explores the significance behind ritual celebrations depicted in the published drinking songs and toasts that emanated from a freemasonic lodge active in the early 1780s in Vienna. Bacchanalian overindulgence within the exclusive association aimed to create a fraternity that would act together to bring progress to Habsburg lands. Publication of their celebrations aimed to bring the same benefits to the rest of the western world. By excluding women, by acting like apes, by singing and chanting formulaic verses while ritually eating and drinking, men became part of a community and found a new identity. Drunken homosocial celebration provided the antidote to the constructed problem of a contemporary society still dominated by aristocratic women or religious institutions. Masons believed their lodge provided them freedom from societal constraints and a social transparency necessary to uncovering a more natural self. The tension inherent in the form of masculinity in the Viennese lodge's songs and toasts, whereby what may be termed the "high" and the "low" mixed, was the basis of freemasonry's appeal and effectiveness. Belly laughter and base behavior were by no means oppositional to a rational program of societal reform. Through these drinking songs and ritual practices, the association emphasized self-improvement and moral development. Publication of their celebrations aimed to bring the same benefits to the rest of the western world. In a time of transformation in social practices and hierarchies, freemasonry taught brothers how to behave as men amongst fellow men and with women. The idealistic intellectual and bacchanalian sociable masculinities combined to allow members to articulate new measures of social worth.

The current state of scholarly communication is presented as one of contest between an increasingly commercial system that is dysfunctional and incompatible with the basic aims of scholarship, and emerging alternatives, particularly open access publishing and open access archiving. Two approaches to facilitating global participation in scholarly communication are contrasted; equity is seen as a superior goal to the donor model, which requires poverty or inequity to succeed. The current state of scholarly communication within the discipline of communication is examined. A relatively healthy percentage of not-for-profit publishers and at least 76 fully open access journals suggest strong potential for emancipating scholarship in communication from commercial imperatives. Specific sites of struggle and actions for scholars, including developing open access journals and self-archiving, are presented.

We evaluated antecedent exercise for treating the automatically reinforced problem behavior of 4 individuals with autism. We conducted preference assessments to identify leisure and exercise items that were associated with high levels of engagement and low levels of problem behavior. Next, we conducted three 3-component multiple-schedule sequences: an antecedent-exercise test sequence, a noncontingent leisure-item control sequence, and a social-interaction control sequence. Within each sequence, we used a 3-component multiple schedule to evaluate preintervention, intervention, and postintervention effects. Problem behavior decreased during the postintervention component relative to the preintervention component for 3 of the 4 participants during the exercise-item assessment; however, the effects could not be attributed solely to exercise for 1 of these participants.

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome.

Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.

Angelo Soliman, a black African, conveyed his heritage and his full participation in eighteenth-century Habsburg society through a mixture of eastern and western dress. As a freemason, Soliman's costume evoked popular conceptions of 'blackness' while asserting his equality within his lodge. Yet the costumes Soliman wore in the service of Prince von Liechtenstein or in the imperial natural history collection, where his stuffed body was placed after death, displayed political power by symbolically subjugating the African. Soliman's daily, Freemasonic, state ceremonial, and post-mortem dress reveal the complex layers of African identity in eighteenth-century Europe.

The advent of policies at research-funding organizations requiring grantees to make their funded research openly accessible alters the life cycle of scholarly research. This survey-based study explores the approaches that libraries and research administration offi ces at the major Canadian universities are employing to support the research-production cycle in an open access era and, in particular, to support researcher adherence to funder open-access requirements. Responses from 21 universities indicated that librarians feel a strong sense of mandate to carry out open access-related activities and provide research supports, while research administrators have a lower sense of mandate and awareness and instead focus largely on assisting researchers with securing grant funding. Canadian research universities already contain infrastructure that could be leveraged to support open access, but maximizing these opportunities requires that research administration offices and university libraries work together more synergistically than they have done traditionally. Normal.dotm 0 0 1 189 1082 The University of British Columbia 9 2 1328 12.0 0 false 18 pt 18 pt 0 0 false false false L’apparition de politiques provenant d’organismes de fi nancement en recherches qui obligent les recipiendaires de rendre les resultats de leur recherche libre a l’acces, a un impacte sur le cycle de vie de la recherche academique. Ce sondage national en ligne explore les mesures prises par les bibliotheques et les administrateurs universitaires de la recherche oeuvrant dans des grandes universites du Canada pour appuyer le cycle de production de recherche dans une ere d’acces libre, et en particulier les mesures appuyant l’adhesion des chercheurs aux exigences d’acces libre de leur agence subventionnaire. Les reponses de la part de 21 universites canadiennes indiquent que les bibliothecaires sont fortement motivees a offrir des activites reliees a l’acces libre ainsi qu’a offrir de l’appui a la recherche, tandis que les administrateurs demontrent un engagement moins eleve a cet egard et se concentrent principalement a aider les chercheurs a obtenir des subventions. Les universites canadiennes de recherche possedent deja des infrastructures pouvant etre exploitees pour soutenir l’acces libre. Cependant, afi n de maximiser ces opportunites, cela necessitera un travail partage entre les bibliothecaires et les administrateurs de la recherche qui est beaucoup plus conjoint qu’anterieurement.

We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations.

We describe a standard star catalog constructed using multiple SDSS photometric observations (at least four per band, with a median of ten) in the $ugriz$ system. The catalog includes 1.01 million non-variable unresolved objects from the equatorial stripe 82 ($|\delta_{J2000}

The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin were labelled immunohistochemically in sections of muscle from commercially available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for several days. Actin, nebulin and spectrin gave similar labelling patterns in both pork and cod muscle which remained the same in stored samples. Desmin was intensely labelled at the cell boundaries and within the body of the cells in both pork and cod in the initial and the stored samples. Vinculin was readily labelled in pork muscle but showed only diffuse labelling in fish. Labelling for talin in pork muscle was intense at the sarcolemma but was not present in samples stored for 4 days. In contrast, the label for talin was concentrated at the myotendinous junction of the cod muscle throughout the storage period. These are the first reports of the detection and location of spectrin and vinculin in fish muscle and of the location of talin. The results are discussed in terms of muscle structure, function and post-mortem tenderisation. © 2000 Society of Chemical Industry.

This article reports the results of an exploratory study using focus group methodology in information literacy research. A small focus group — seven undergraduate students at Concordia University College of Alberta — discussed the concept of information literacy and the role of the undergraduate library in developing information literacy skills. Participants perceived information literacy as valuable, and agreed that the library plays an important role in developing the skill of locating information. Moreover, the focus group method demonstrated potential for generating useful data in this field, particularly hypotheses for further research.