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We revisit the problem of tabulating Carmichael numbers. Carmichael numbers have been tabulated up to 10 21 using an algorithm of Pinch (Math Comp 61(203):381–391, 1993). In finding all Carmichael numbers with d prime factors, the strategy is to first construct pre-products P with d - 2 prime factors, then find primes q and r such that Pqr satisfies the Korselt condition. We follow the same general strategy, but propose an improvement that replaces an inner loop over all integers in a range with a loop over all divisors of an intermediate quantity. This gives an asymptotic improvement in the case where P is small and expands the number of cases that may be accounted as small. In head-to-head timings this new strategy is faster over all pre-products in a range, but is slower on prime pre-products. A hybrid approach is shown to improve even the case of prime pre-products. [ABSTRACT FROM AUTHOR]

Secondary hematologic malignancies, such as B-cell acute lymphoblastic leukemia/lymphoma (B-ALL), have been reported following multiple myeloma. Tyrosine kinase inhibitors have improved clinical outcomes of patients with Philadelphia-positive (Ph+) B-ALL. Therefore, recognition of the Ph chromosome in B-ALL patients is important for both prognosis and therapies. We present a case of a secondary Ph+ B-ALL following multiple myeloma that highlights a BCR::ABL1 fusion by a gene fusion assay to reveal a cryptic Ph chromosome, which may otherwise be missed by conventional cytogenetics and typical interphase fluorescence in situ hybridization. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To understand the importance of an effective workplace culture in older people's care settings • To learn about the 'Guiding Lights for effective workplace cultures' and how they can support staff and patients to feel safe and valued • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers) While much attention has been given to organisational culture, there has been less focus on workplace culture. Yet workplace culture strongly influences the way care is delivered, received and experienced. An effective workplace culture is crucial for the well-being of individual staff members and teams as well as for patients' experiences and outcomes of care. This article describes the 'Guiding Lights for effective workplace cultures' which were developed by the authors and provide a framework to assist in understanding and promoting effective workplace cultures and creating environments where staff and patients feel safe and valued. There are four Guiding Lights: 'collective leadership', 'living shared values', 'safe, critical, creative learning environments' and 'change for good that makes a difference'. Each one articulates what good workplace cultures are through descriptors and intermediate outcomes and together produce a set of ultimate outcomes. The Guiding Lights provide nurses working in older people's care settings with an opportunity to learn from, and celebrate, what is going well in their workplaces and to consider areas that require further development. [ABSTRACT FROM AUTHOR]

Relapse is the most common cause of treatment failure following allogeneic blood or marrow transplantation (alloBMT) for AML or MDS. Post-transplant maintenance therapies may prevent relapse. We conducted a phase II trial combining azacitidine (AZA) with GM-CSF in non-relapsed, post-transplant patients with AML or MDS. Patients received escalating doses of AZA to a maximum of 75 mg/m2 for 5 days per cycle for up to 12 cycles. GM-CSF was given on days 1–10 of each cycle. Eighteen patients were treated following non-myeloablative (17) and myeloablative (1) alloBMT for AML (61.1%), MDS (27.7%), or therapy-related myeloid neoplasm (11.1%). The majority of patients (72%) received their graft from an HLA-haploidentical donor. The treatment was well-tolerated with rare grade 3–4 hematologic toxicities. One patient suffered an exacerbation of GVHD. The 24-month relapse-free and overall survivals were 47 and 57%, respectively, with a median of 18.6 and 29 months. [ABSTRACT FROM AUTHOR]

Let k ≥ 1 be an integer, and let P = (ƒ1(x), . . ., ƒk(x)) be k admissible linear polynomials over the integers, or the pattern. We present two algorithms that find all integers x where max {ƒi(x)} ≤ n and all the ƒi(x) are prime. Our first algorithm takes OP(n/(log log n)k) arithmetic operations using O(k√n) space. Our second algorithm takes slightly more time, OP(n/(log log n)k-1) arithmetic operations, but uses only n1/c space for c > 2 a fixed constant. The correctness of this algorithm is unconditional, but our analysis of its running time depends on two reasonable but unproven conjectures. We are unaware of any previous complexity results for this problem beyond the use of a prime sieve. We also implemented several parallel versions of our second algorithm to show it is viable in practice. In particular, we found some new Cunningham chains of length 15, and we found all quadruplet primes up to 1017. [ABSTRACT FROM AUTHOR]

Michael Halliday once stated that all theories employ metaphors in order to express their essence, which might be restated as 'every theory is a myth for what it is theorizing'. In his early work, Braj Kachru set out to creatively and critically 'de‐mythologize' the English canon, and in its stead introduced the new metaphor of the 'Three Circles', and the innovative, and redeeming, myth of 'world Englishes', changing the history of English studies in the process. [ABSTRACT FROM AUTHOR]

Abstract Purpose In light of recently published guidelines from the US Food and Drug Administration (FDA) on the communication of real-world data (RWD) and real-world evidence (RWE) to support regulatory decision making, it is important to understand how such data are developed, the limitations of these data, and how to best use RWD to improve patient care. Historically, the use of RWE has been approached with skepticism because of its often-retrospective nature compared with data from conventional randomized controlled trials (RCTs). This review discusses the role and function of RWE and RWD in clinical research. We summarize the types of RWE used in clinical research, outline the challenges and limitations involved with these data, and suggest how these types of analyses can supplement results from clinical trials to foster a more complete understanding of a drug or disease area of interest. In particular, we focus on the role of RWE in investigating chronic myeloid leukemia (CML) and tyrosine kinase inhibitor therapy for CML. Methods We reviewed FDA guidance on the use of RWE and conducted a PubMed literature search to evaluate published data from real-world studies in CML. Findings RWE includes analysis of RWD gathered from nonconventional sources, including patient registries, observational studies, and social media, among others. Importantly, although real-world studies do not adhere to the same degree of controlled conditions and predefined patient-management strategies as do conventional clinical trials, analyses resulting from these studies can be held to a high degree of validation and standardization, making them as meaningful as those from RCTs. In CML, RWE has informed early treatment milestones and has provided a window into patient perspectives regarding treatment. These types of analyses have already informed and can continue to inform disease management. These improvements in disease management, in turn, will help clinicians to better forecast treatment challenges and allow for the optimization of future treatment paradigms. Implications Real-world studies are different from conventional RCTs and therefore provide insight into distinct aspects of treatment and patient outcomes. Together with results from clinical trials, RWE can help to illustrate a more complete picture of the tolerability, effectiveness, and impact of a drug. The recently published guidelines indicate that the FDA expects a growing role for RWE. [ABSTRACT FROM AUTHOR]

Edwin Thumboo's poem Language as Power, written for Larry and Braj (L&B) provides the central theme for this paper written in remembrance of Larry. The poem is a composition in two movements, engaging readers aesthetically and spiritually. The poem's first movement is more like a hymn, celebrating the power of the Word. The second movement explores the impact of the phenomenon known as world Englishes. The paper concludes with two personal notes: the first explaining how the meaning‐making potential of language – what Halliday calls 'grammatical energy' – is employed by the poet to immortalize L & B; and the second, how our encounters with Larry's every good endeavor have enriched our lives and made us better human beings. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) therapies are rapidly evolving with novel targeted therapies showing high-level responses in a notoriously difficult to treat group of patients – the elderly and unfit. This review will examine the outcomes of older AML patients (>60 years old) with conventional induction strategies, and published literature on risks of pursuit of induction. Low-intensity combination therapy response rates appear to be approaching that of induction regimens, and with lower toxicity, low-intensity therapy likely represents the future standard approach in this age group. Lastly, allogeneic transplant appears to have a role in increasing durable remissions regardless of age and should be considered in patients with limited comorbidities. [ABSTRACT FROM AUTHOR]

Purpose Cytosine arabinoside (AraC) remains the backbone of most treatment regimens for acute myeloid leukemia (AML). Incorporation of AraC into DNA activates checkpoint kinase 1 (Chk1), leading to cell-cycle arrest and diminished AraC cytotoxicity, which can be reversed by the selective Chk1 inhibitor MK-8776. Building on a Phase I trial, we conducted a phase II trial comparing timed sequential AraC with or without MK-8776. Methods Patients with relapsed or primary refractory AML were randomized 1:1 to receive either AraC with MK-8776 (Arm A); or AraC alone (Arm B). Results 32 patients were treated: 14 assigned to Arm A and 18 to Arm B. There were 5 (36%) complete responses (CR/CRi) and 1 (7%) partial response (PR) in Arm A, and 8 (44%) CR/CRis and 1 (6%) PR in Arm B. Median survival did not differ significantly between the two groups (5.9 months in Arm A vs. 4.5 months in Arm B). MK-8776 led to a robust increase in DNA damage in circulating leukemic blasts as measured by increased γ-H2AX (16.9% ± 6.1% prior and 36.4% ± 6.8% at one hour after MK-8776 infusion, p = 0.016). Conclusion Response rates and survival were similar between the two groups in spite of evidence that MK-8776 augmented DNA damage in circulating leukemic blasts. Better than expected results in the control arm using timed sequential AraC and truncated patient enrollment may have limited the ability to detect clinical benefit from the combination. [ABSTRACT FROM AUTHOR]

This paper offers a strategic initiative designed to boost the level of collaborative mathematical research involving undergraduate mathematics students at Butler University. It describes goals, program design, logistics, and outcomes for an 8-day intensive summer experience in which undergraduate mathematics majors engaged in original mathematical research at an introductory level. [ABSTRACT FROM AUTHOR]

Let ψm be the smallest strong pseudoprime to the first m prime bases. This value is known for 1 ≤ m ≤ 11. We extend this by finding ψ12 and ψ13. We also present an algorithm to find all integers n ≤ B that are strong pseudoprimes to the first m prime bases; with reasonable heuristic assumptions we can show that it takes at most B2/3+o(1) time. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen–Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure–activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones’ effects to rescue neurons subjected to ROS-induced stress created by the addition of β-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class. [ABSTRACT FROM AUTHOR]

• Adjuvant interferon-α/GM-CSF and K562/G-CSF vaccine were safe with TKIs. • Patients more frequently discontinued interferon-α/GM-CSF due to side effects. • Adjuvant interferon-α/GM-CSF more frequently led to undetectable BCR-ABL PCR. • 36.4 % of patients sustained treatment-free remission after interferon-α/GM-CSF. Chronic myeloid leukemia (CP-CML) patients can achieve undetectable minimal residual disease (UMRD) and discontinue tyrosine kinase inhibitors (TKIs). Cellular immunity plays an important role in CML disease control. We conducted a randomized, non-blinded phase II trial of adjuvant immunotherapy with TKIs to facilitate TKI discontinuation. TKI-treated patients with CP-CML were randomized to receive the K562/GM-CSF vaccine (vaccine) OR Interferon-α + Sargramostim (IFN). If UMRD was achieved, then all treatment was stopped. Patients who did not achieve UMRD within one year, had a molecular relapse, or discontinued therapy for toxicity could crossover. Thirty-four patients were randomized to IFN (n = 18) or vaccine (n = 16), and 21 patients crossed over (IFN⟶vaccine: n = 9, vaccine⟶IFN, n = 12). TKIs at enrollment included imatinib (n = 31), nilotinib (n = 2), and dasatinib (n = 1). No patients discontinued vaccine due to side effects, while 33 % of IFN-treated patients discontinued treatment. More patients randomized to IFN (47.4 %, 95 % CI: 16.7–66.7 %) versus vaccine (25.0 %, 95 % CI: 0.5–43.5 %) achieved UMRD within one year. Seven patients randomized to IFN discontinued treatment with 28.6 % (95 % CI: 8.9–92.2 %) sustaining treatment-free remission (TFR) at 1 year, while three patients randomized to vaccine discontinued treatment with none sustaining TFR. Including crossover, there was a cumulative discontinuation success rate of 36.4 % (95 % CI: 16.6 %–79.5 %) after adjuvant IFN. Patients who sustained TFR received a median of 29 months of imatinib prior to discontinuation. Adjuvant IFN led to durable TFRs with limited prior TKI exposure with comparable success to prior discontinuation trials, but many patients stopped IFN early. [ABSTRACT FROM AUTHOR]

There is something inexplicable about our potential for ceaseless creativity, in both the making and the reading of meaning, not just in poetry, or some other form of verbal art, but in every aspect of our lives. In 'A poet reading', the poet Edwin Thumboo explores our capacity for ceaseless creativity in language with a poem whose meaning is bounded only by whatever readings the grammar will allow. Reading 'A poet reading', the linguist attempts a 'raid on the inarticulate', to gain insight into the reality-generating power and creative energy of grammar as system of meaning potential. [ABSTRACT FROM AUTHOR]

This article encourages nurses working with older people in general hospital settings to reflect critically on their practice relating to nutritional care. Some approaches to developing practice in the nutritional care of older people are identified. INSETS: Case study 1;Case study 2. [ABSTRACT FROM AUTHOR]

This article describes how a programme of practice development enabled practitioners working within an acute health services provider organization to develop practice through joint learning with older people focused on dignity in care using creative arts. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This article reports an attempt to investigate, apart from the semantics and the pragmatics, how much the lexis and the grammar of a conversation can help extract interpersonal information about the interlocutors' orientations towards each other. The discourse analysed was extracted from a scene in Dan Brown's novel The Da Vinci Code and its motion picture adaptation. The adaptation of this scene is similar to the novel original in terms of the characters' content of discussion and only differs in the orientation of the characters to one another. The analysis focuses on the determination of response types, which are generally classified as either expected or discretionary, and contribute to the realization of positive and negative orientations respectively. The distribution of different types of response is visualized as the interlocutor's 'response profile', which helps in the realization of his/her orientation to the one to whom he/she is responding. [ABSTRACT FROM AUTHOR]

The article presents a response to the article related to the development of patient experience definition and strategy to inform clinical commissioning in London, England, and suggests an approach for the strategy that is evidence based, collaborative and continuous.

This article describes the process of ‘growing’ a practice development strategy for three community hospitals managed by a primary care trust through joint working with the Royal College of Nursing Practice Development Team. It focuses on the early process of developing the strategy, up until the implementation stage. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The focus of this linguistic investigation is on the poetry of Edwin Thumboo, which has contributed much to the shaping and definition of Singapore's English language poetic canon. A systemic-functional approach is adopted for analysing several of Thumboo's poems, including “gods can die”, “David”, and “Conjunction”, examining the poet's technique, or, as in the poet's own words, “the chiseling of Language, the rearranging of language, the sound, the rhythm, the tautness, the layering”. Linguistic analysis of Edwin Thumboo's poetry reveals an imagery projected through the poet's technique, in combination with metaphorical allusions to science, theology, mythology, and even numerology. Each of his poems is a highly textured, grammatically intricate work of art with multiple layers of meaning and metaphor. [ABSTRACT FROM AUTHOR]

This article describes the principles behind the assessment of older people's needs and the challenges inherent in developing a person-centred framework for assessment. It suggests that person-centred assessment calls for skilled, empowered and well-supported nurses who are able to work in creative, innovative ways and who recognise that the needs of the older person are at the centre of all therapeutic working. [ABSTRACT FROM AUTHOR]

In this paper we report on our recent work in clause alignment for English-Chinese bilingual legal texts using available lexical resources including a bilingual legal glossary and a bilingual dictionary, for the purpose of acquiring examples at various linguistic levels for example-based machine translation. We present our formulation of an appropriate measure for the similarity of a candidate pair of clauses with respect to matched lexical items and the corresponding implementation of an effective algorithm for clause alignment based on this similarity measure. Experimental results show that the similarity measure and the lexical-based clause alignment algorithm, though very simple, are very effective, with a performance of 94.6% alignment accuracy. It confirms our intuition that lexical information gives a reliable indication of correct alignment. The significance of this lexical-based approach lies in both its simplicity and effectiveness. [ABSTRACT FROM AUTHOR]

Focuses on ways in which reflective practice can help nurses develop their care of older people. Development of the insight of individual into professional practice and therapeutic relationships; Barriers to reflective writing. INSET: An illustration of reflective pratice.

Focuses on definitions and descriptions of team-working in the care of older people. Importance of education, clear leadership and national support to develop multiprofessional approaches; Changes in the delivery of health care to meet the diverse needs of service users; Concept of teamwork within the primary care.

Background: The Covid-19 pandemic has created an unprecedented challenge for health and social care systems globally. There is an urgent need for research on experiences of COVID-19 at different levels of health systems, including lessons from professional, organisational and local system responses, that can be used to inform managerial and policy responses. Methods: This paper presents the findings from a thematic analysis of front-line staff experiences working across the Norfolk and Waveney integrated care system (ICS) in the East of England during April and October 2020 to address the question "What are the experiences and perceptions of partner organisations and practitioners at multiple levels of the health system in responding to COVID-19 during the first wave of the pandemic?" This question was posed to learn from how practitioners, interdependent partner organisations and the system experienced the pandemic and responded. 176 interview transcripts derived from one to one and focus group interviews, meeting notes and feedback from a "We Care Together" Instagram campaign were submitted for qualitative thematic analysis to an external research team at a regional University commissioned to undertake an independent evaluation. Three phases of qualitative analysis were systematically undertaken to derive the findings. Findings: Thirty-one themes were distilled highlighting lessons learned from things that went well compared with those that did not; challenges compared with the celebrations and outcomes; learning and insights gained; impact on role; and system headlines. The analysis supported the ICS to inform and capitalise on system wide learning for integration, improvement and innovations in patient and care home resident safety, and staff wellbeing to deal with successive waves of the pandemic as well as prioritising workforce development priorities as part of its People Plan. Conclusions: The findings contribute to a growing body of knowledge about what impact the pandemic has had on health and social care systems and front-line practitioners globally. It is important to understand the impact at all three levels of the system (micro, meso and macro) as it is the meso and macro system levels that ultimately impact front line staff experiences and the ability to deliver person centered safe and effective care in any context. The paper presents implications for future workforce and health services policy, practice innovation and research. [ABSTRACT FROM AUTHOR]

ABSTRACT: The poetry of Edwin Thumboo has contributed much to the shaping and definition of Singapore's English Language poetic canon. In this paper, I explore Thumboo's esthetic use of consistent foregrounding in the poem gods can die from three perspectives: propositional, textual and interpersonal. Foregrounding refers to the usage of certain linguistic devices for the purpose of attracting attention. In poetry, meaning and esthetic effect are unified through the poet's deliberate and systematic foregrounding of linguistic devices. Juxtaposed against the backgrounds of the standard language and an often rich and diverse poetic canon, the poet asserts his individuality through the systematic foregrounding of relations between the functional semantic components that together comprise the poem as semiotic object. The approach adopted here is functional-semantic in orientation and based on earlier work carried out by the Prague School and more recently by Michael A. Halliday and Ruqaiya Hasan. While it may be argued that the totality of the poet's message is unlikely to be ever fully captured by even the most careful and detailed linguistic analysis, nevertheless this should not prevent one from attempting to explore the linguistic intricacy of the poet's handiwork. For from such analysis, we gain an even better appreciation of the texture and meaning of the poem. [ABSTRACT FROM AUTHOR]

Background: The Covid-19 pandemic has created an unprecedented challenge for health and social care systems globally. There is an urgent need for research on experiences of COVID-19 at different levels of health systems, including lessons from professional, organisational and local system responses, that can be used to inform managerial and policy responses.Methods: This paper presents the findings from a thematic analysis of front-line staff experiences working across the Norfolk and Waveney integrated care system (ICS) in the East of England during April and October 2020 to address the question "What are the experiences and perceptions of partner organisations and practitioners at multiple levels of the health system in responding to COVID-19 during the first wave of the pandemic?" This question was posed to learn from how practitioners, interdependent partner organisations and the system experienced the pandemic and responded. 176 interview transcripts derived from one to one and focus group interviews, meeting notes and feedback from a "We Care Together" Instagram campaign were submitted for qualitative thematic analysis to an external research team at a regional University commissioned to undertake an independent evaluation. Three phases of qualitative analysis were systematically undertaken to derive the findings.Findings: Thirty-one themes were distilled highlighting lessons learned from things that went well compared with those that did not; challenges compared with the celebrations and outcomes; learning and insights gained; impact on role; and system headlines. The analysis supported the ICS to inform and capitalise on system wide learning for integration, improvement and innovations in patient and care home resident safety, and staff wellbeing to deal with successive waves of the pandemic as well as prioritising workforce development priorities as part of its People Plan.Conclusions: The findings contribute to a growing body of knowledge about what impact the pandemic has had on health and social care systems and front-line practitioners globally. It is important to understand the impact at all three levels of the system (micro, meso and macro) as it is the meso and macro system levels that ultimately impact front line staff experiences and the ability to deliver person centered safe and effective care in any context. The paper presents implications for future workforce and health services policy, practice innovation and research. [ABSTRACT FROM AUTHOR]

Background: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK‐228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. Methods: We conducted a single‐arm multi‐center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI‐9775). Results: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), were enrolled. Major grade 3–4 non‐hematologic toxicities included mucositis (3 patients) and hyperglycemia (2 patients) as well as hepatic failure, seizures, confusion, pneumonitis, and anorexia (1 patient each). Grade >2 hematological toxicity included leukopenia (3), lymphopenia (2), thrombocytopenia, and neutropenia (1). The best response was stable disease in 2 patients (12.5%), while only 3 patients (19%) were able to proceed to Cycle 2. Pharmacokinetic analysis demonstrated drug exposures similar to those observed in solid tumor patients. Immunoblotting in serially collected samples indicated limited impact of treatment on phosphorylation of mTOR pathway substrates such as 4EBP1, S6, and AKT. Conclusion: In summary, single‐agent sapanisertib had a good safety profile but limited target inhibition or efficacy in ALL as a single agent. This trial was registered at ClinicalTrials.gov as NCT02484430. [ABSTRACT FROM AUTHOR]

First published in 2005, this book has been extensively updated. It challenges the use of psychiatric diagnoses and makes the case for person-centred approaches as alternative ways to work with people who would otherwise be diagnosed with severe mental illnesses. [ABSTRACT FROM AUTHOR]

Although DNA methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used extensively in the treatment of myelodysplastic syndromes and acute myeloid leukemia, there remain unanswered questions about DNMTi's mechanism of action and predictors of clinical response. Because patients often remain on single‐agent DNMTis or DNMTi‐containing regimens for several months before knowing whether clinical benefit can be achieved, the development and clinical validation of response‐predictive biomarkers represents an important unmet need in oncology. In this review, we will summarize the clinical studies that led to the approval of azacitidine and decitabine, as well as the real‐world experience with these drugs. We will then focus on biomarker development for DNMTis—specifically, efforts at determining exposure–response relationships and challenges that remain impacting the broader clinical translation of these methods. We will highlight recent progress in liquid‐chromatography tandem mass spectrometry technology that has allowed for the simultaneous measurement of decitabine genomic incorporation and global DNA methylation, which has significant potential as a mechanism‐of‐action based biomarker in patients on DNMTis. Last, we will cover important research questions that need to be addressed in order to optimize this potential biomarker for clinical use. [ABSTRACT FROM AUTHOR]

The article presents the response of various consultant nurses to a question enquiring whether the holistic approach in nursing in Great Britain has collapsed resulting in fragmentation of care and whether the changing role of nurses contributes toward this downfall. One of the nurses disagree with the assumption that the holistic approach has collapsed. Another nurse points that with technical advances in medicine there is a need for nurses to develop skills in their area of expertise.

This article presents matters related to a forum for nurse consultants working for older people. Ask the experts is a forum in which nurse consultants working with older people debate an issue in older people's care and offer advice. By April 2005 all local health and social care systems were to have established an integrated falls service. The question arises that as nurses how one can ensure that falls and falls-prevention services continue to develop after this date to ensure best practice for older people.

The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups. [ABSTRACT FROM AUTHOR]

The article reflects on best practice in clinical medicine. Clinical practice is considered multifaceted because there is nothing basic about working with and caring for people who have complicated age-related needs. Poor clinical practice is said to cause a number of interrelated clinical governance problems at all levels across an organisation. Also fundamental to best practice is an effective work-based culture that enables innovation.

The article claims that nurses caring for older people need to be prepared to face the challenges in the service. It notes that the first standard identified by the National Service Framework (NSF) for Older People is the eradication of age discrimination in healthcare. It cites the important role played by nurses related to the use of acute services by older people. It adds that nurses should have the skills to recognise and manage acute and chronic needs.

The article expresses the author's opinions regarding the impact that leaders have in the care of older people. Efforts by the Health Minister of Great Britain, Ara Warkes Darzi, in developing leaders involved with the care of older people are discussed. The roles in which Darzi feels that leaders can play in the care of older people are mentioned, including to promote care that is centered around the person.

Older people do not lose their individuality when they become patients. Using autobiography, which is written or told by the person and biography written or told by someone else, during the process of assessment can enable nurses to 'see' the real person behind the patient. The life history can help form or shape the development and maintenance of a personal identity. This influences the way, nurses can work in partnership with older people and their supporters. Equally important, older people should not be made to fit into rigid, unbending assessment frameworks. The method of assessment should be designed around the people's needs and personal priorities and should reflect the older person's right to independence and choice. INSET: Box 1.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12913-022-07797-7. [ABSTRACT FROM AUTHOR]

There are currently no known predictors of myelodysplastic syndrome (MDS)/myeloproliferative overlap neoplasm (MPN) patients' response to hypomethylating agents (HMA). Forty-three patients with MDS/MPN who were treated with HMA during chronic phase and had next-generation sequencing using the established 63-genes panel were identified. Complete and partial remission and marrow response were assessed based on the MDS/MPN International Working Group response criteria. On univariate analysis, younger age, higher number of mutations, and mutations in SETBP1, RUNX1, or EZH2 were associated with no response. Multivariable analysis for modeling response were conducted via least absolute shrinkage and selection operator logistic regression approach, and showed that mutations in SETBP1, RUNX1, or EZH2 predict lack of HMA response. While limited by sample size, our findings suggest that genomic landscape can potentially identify MDS/MPN patients with lower likelihood of response to HMA. [ABSTRACT FROM AUTHOR]

The article focuses on a research work conducted to develop a shared definition of patient experience and strategy that will influence clinical commissioning, by engaging with patients, health care workers and service users in North-West London, England.

Background: Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. Methods: A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. Results: Stable normoprolactinemia was achieved in 186 of the 223 women treated with cabergoline (83 percent) and 138 of the 236 women treated with bromocriptine (59 percent, P<0.001). Seventy-two percent of the women treated with cabergoline and 52 percent of those treated with bromocriptine had ovulatory cycles or became pregnant during treatment (P<0.001). Amenorrhea persisted in 7 percent of the cabergoline-treated women and 16 percent of the bromocriptine-treated women. Adverse effects were recorded in 68 percent of the women taking cabergoline and 78 percent of those taking bromocriptine (P = 0.03); 3 percent discontinued taking cabergoline, and 12 percent stopped taking bromocriptine (P<0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the women treated with cabergoline. Conclusions: Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea. (N Engl J Med 1994;331:904-9.) [ABSTRACT FROM AUTHOR]

Chinese news texts often contain a number of abbreviations without explicitly defining their full-forms. Therefore, expanding abbreviations to their original full-forms plays an important role in improving accuracy of the information extraction and retrieval systems for Chinese. In this paper, we present a hybrid approach to automatic expansion of abbreviations in Chinese news texts. Generally, Chinese abbreviations are produced from their original full-forms via reduction, elimination or generalization. To ensure every abbreviation can successfully be expanded, each abbreviation under expansion is assumed to be created by these three methods, respectively. Based on this assumption, a mapping table between shortened words and their matrix words, and a dictionary of short-form/full-form pairs are used to generate all possible expansions for abbreviations. For an ambiguous abbreviation with mutiple expansion candidates, then hidden Markov models are employed to rank all its expansion candidates and select a proper one with the maximum score. In order to further improve expansion performance, some linguistic knowledge like discourse information and abbreviation patterns are utilized to correct possible expansion errors. Evaluation on an abbreviation-expanded corpus built from the Peking University Corpus showed that our approach can achieve 86.3% and 83.8% on average in precision and recall respectively for various types of abbreviations in Chinese news texts. [ABSTRACT FROM AUTHOR]