Reading, writing and apprenticeships: developing an authentic reading and assessment strategy for graduate apprenticeships.

The recent launch of graduate apprenticeships in Scotland requires participating universities to collaborate closely with employers to design and develop innovative curricula to enable apprentices to acquire new knowledge and develop relevant skills both in a traditional university learning and teaching setting as well as in the workplace. This paper argues that the additional context of learning situated in the workplace provides a particular impetus to consider and reflect the requirement and deployment of authentic reading strategies and authentic assessment regimes as essential design elements in these programmes. We present a discussion of the approach we are adopting to designing curricula and preparing learning and assessment resources for graduate apprenticeships in Business Management and Business Management: Financial Services. We focus here specifically on our plans for helping apprentices on these programmes to navigate the plethora of information resources available to them and develop effective reading strategies and information literacy skills in both academic and professional contexts. We indicate how the enhancement of these skills forms an important precursor to tackling the authentic assessments designed for apprentices to evidence their professional and academic learning during their apprenticeships. Our planning and design activity draws first on aspects of our recent research into reading skills and strategies among professionals and business students, as well as on our established track record of delivering a variety of work-based learning programmes. It is envisaged that findings and lessons learned from our work will help guide and inform other institutions across the UK as they establish curricula for graduate or degree apprenticeships

Sorting “Natives” from “Indians” : interrogating historic burials in the Catholic Burying Ground on the Dartmouth Common (1835-1865)

vi, 111 leaves : illustrations (some colour), colour map ; 29 cmIncludes abstract and appendices.Includes bibliographical references (leaves 100-111).This research disrupts a colonial narrative about settlers and hundreds of “Indians” inscribed on a monument as part of a non-Indigenous tourism scheme to raise money and clean up the abandoned Catholic Burying Ground on the Dartmouth Common. Many Natives of Ireland and others, not Natives of North America, are identified by a detailed analysis of handwritten death records and other sources. They were all but forgotten when the municipality took control of the cemetery in 1975 without a copy of the church records. This left a gap in public memory that allowed variations of an “old Indian burial ground” narrative to evolve from burials in the ground (1962) to burials in a mound (2010). The findings are relevant to the national project of Truth and Reconciliation and serve as a cautionary tale about the importance of seeking truth before reconciliation. This research will be of interest to Irish researchers and descendants of those who died; residents of Halifax Regional Municipality who own the cemetery in trust; government administrators, planners, and surveyors; Catholic organizations in control of historic records; and to social, legal and Indigenous researchers who grapple with constructed “Indian” identities as a way of decolonizing the story of Canada

Automated Reminders to Promote Radon Testing in a Lung Cancer Case Control Study

One of the four pilot projects of the Lung Cancer Initiative sponsored by the Department of Defense measures radon levels in the participants homes. Radon exposure is the second leading cause of Lung Cancer. The case-control study has a targeted accrual of 1800 with a case-control ratio of 1:4. The long-term radon kits remain in the home for 90 days and the participants are asked to mail the test kit to the company for analysis. In order to maximize the test kit return rate, reminder calls to the participants occurred 90 days after the home visit

Influence of cytogenetic abnormalities on outcome after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission

AbstractCytogenetic abnormalities detected at diagnosis are recognized as important in predicting response to chemotherapy in acute myeloid leukemia (AML). However, there is controversy concerning the prognostic significance of karyotype for outcome after allogeneic bone marrow transplantation (allo-BMT) performed in first complete remission (CR1). This single-institution report describes allo-BMT for AML in CR1 and the effect of diagnostic cytogenetic findings on the results of that treatment. Between August 1981 and December 1999, 93 patients underwent related donor (n = 82) or unrelated donor (n = 11) BMT. Conditioning and GVHD prophylaxis were achieved predominantly with busulfan and cyclophosphamide and with cyclosporine and methotrexate, respectively. Seventy-nine (85%) of 93 patients had successful marrow karyotyping at diagnosis, and the patients were categorized into 3 prognostic groups based on the British Medical Research Council AML 10 trial classification: 15 patients(19%) were classified as having favorable risk [inv(16), t(8;2 1), t(15;17)]; 55 (70%) as having intermediate risk [no abnormality, +8, +21, +22, del(7q), del(9q), 11q23 rearrangement, and other numerical or structural abnormalities]; and 9 (11%) as having adverse risk [-5, del(5q), -7, 3q rearrangements, > or = 5 abnormalities, t(6;9), t(9;22)]. The median follow-up was 93 months (range, 16-241 months). The overall survival (OS) rate, event-free survival (EFS) rate, relapse rate, and treatment-related mortality (TRM) were not statistically different between the groups. The 5-year actuarial EFS rates for favorable, intermediate, and adverse risk groups were 58% (95% confidence interval [CI], 29%-79%), 58% (95% CI, 43%-70%), and 67% (95% CI 28%-88%), respectively. Reclassification of patients into cytogenetic prognostic subgroups according to Southwest Oncology Group criteria did not change these results. In univariate analysis, the only variable found to have a prognostic influence on OS (P = .04) and TRM (P = .03) was the type of donor (unrelated donor was linked to a worse prognosis), which was confirmed in multivariate analysis. Our study suggests that presentation karyotype has less prognostic significance for outcome following allo-BMT than for outcome following conventional chemotherapy. In particular, AML patients with poor prognostic cytogenetic changes in CR1 who are unlikely to be cured with chemotherapy alone may benefit from allo-BMT.Biol Blood Marrow Transplant 2002;8(8):435-43

Early Stem Cell Transplantation for Refractory Acute Leukemia after Salvage Therapy with High-Dose Etoposide and Cyclophosphamide

AbstractPrimary refractory acute leukemia (AL) has a poor prognosis, although some patients can be salvaged with allogeneic stem cell transplantation (SCT). Induction of complete remission (CR) with conventional chemotherapy before SCT may improve outcome in this patient population. Between March 1991 and October 2003, 59 adults with primary refractory AL were treated with continuous-infusion etoposide (VP) 2.4 to 3.0 g/m2 followed by cyclophosphamide (Cy) 6.0-7.2 g/m2 intravenously over 3 to 4 days with the intention of proceeding to SCT in CR1. Forty-two patients had acute myelogenous leukemia (AML), 13 patients had acute lymphoblastic leukemia (ALL), and 4 patients had acute biphenotypic leukemia. The most frequent nonhematologic toxicities were oral mucosal, gastrointestinal, and hepatic toxicities (44%, 20%, and 15% of patients, respectively). Thirty-two (57%) of 56 evaluable patients entered CR1 with a median time to platelet and neutrophil recovery of 22 and 26 days, respectively. CR1 rates were similar in AML (54%) and ALL/acute biphenotypic leukemia (67%; P = .52), and analysis of baseline characteristics did not reveal any predictors of response to VP/Cy. Twenty-nine of 32 CR1 patients subsequently underwent SCT (24 allogeneic and 5 autologous). Estimated 5-year event-free survival (EFS) and overall survival for the entire cohort are 23% and 26%, respectively. In the allogeneic SCT group, 5-year EFS was 52% for AML patients and 14% for ALL patients (P = .04), and only male sex was predictive of a favorable outcome (P = .03). VP/Cy is able to induce CR1 in most patients with primary refractory AL with an acceptable toxicity profile. Subsequent allogeneic SCT can lead to long-term EFS in a significant proportion of patients

Time to integrate global climate change and biodiversity science‐policy agendas

Funder: Research EnglandFunder: Bertarelli FoundationAbstract: There is an increasing recognition that, although the climate change and biodiversity crises are fundamentally connected, they have been primarily addressed independently and a more integrated global approach is essential to tackle these two global challenges. Nature‐based Solutions (NbS) are hailed as a pathway for promoting synergies between the climate change and biodiversity agendas. There are, however, uncertainties and difficulties associated with the implementation of NbS, while the evidence regarding their benefits for biodiversity remains limited. We identify five key research areas where incomplete or poor information hinders the development of integrated biodiversity and climate solutions. These relate to refining our understanding of how climate change mitigation and adaptation approaches benefit biodiversity conservation; enhancing our ability to track and predict ecosystems on the move and/or facing collapse; improving our capacity to predict the impacts of climate change on the effectiveness of NbS; developing solutions that match the temporal, spatial and functional scale of the challenges; and developing a comprehensive and practical framework for assessing, and mitigating against, the risks posed by the implementation of NbS. Policy implications. The Conference of the Parties (COP) for the United Nations Framework Convention on Climate Change (COP26) and the Convention on Biological Diversity (COP15) present a clear policy window for developing coherent policy frameworks that align targets across the nexus of biodiversity and climate change. This window should (a) address the substantial and chronic underfunding of global biodiversity conservation, (b) remove financial incentives that negatively impact biodiversity and/or climate change, (c) develop higher levels of integration between the biodiversity and climate change agendas, (d) agree on a monitoring framework that enables the standardised quantification and comparison of biodiversity gains associated with NbS across ecosystems and over time and (e) rethink environmental legislation to better support biodiversity conservation in times of rapid climatic change

ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer.

We have previously shown that during pregnancy the E-twenty-six (ETS) transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER)-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq). ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance

Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial

BACKGROUND: New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma. METHODS: In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age ≥18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126. FINDINGS: The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2-14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last line of therapy. Overall responses were noted in 31 patients (29.2%, 95% CI 20.8-38.9)-three (2.8%, 0.6-8.0) had a stringent CR, ten (9.4%, 4.6-16.7) had a very good PR, and 18 (17.0%, 10.4-25.5) had a PR. The median time to first response was 1.0 month (range 0.9-5.6). Median duration of response was 7.4 months (95% CI 5.5-not estimable) and progression-free survival was 3.7 months (95% CI 2.8-4.6). The 12-month overall survival was 64.8% (95% CI 51.2-75.5) and, at a subsequent cutoff, median overall survival was 17.5 months (95% CI 13.7-not estimable). Daratumumab was well tolerated; fatigue (42 [40%] patients) and anaemia (35 [33%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation. INTERPRETATION: Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients. FUNDING: Janssen Research & Development

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk