238 research outputs found

    A time predefined variable depth search for nurse rostering

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    This paper presents a variable depth search for the nurse rostering problem. The algorithm works by chaining together single neighbourhood swaps into more effective compound moves. It achieves this by using heuristics to decide whether to continue extending a chain and which candidates to examine as the next potential link in the chain. Because end users vary in how long they are willing to wait for solutions, a particular goal of this research was to create an algorithm that accepts a user specified computational time limit and uses it effectively. When compared against previously published approaches the results show that the algorithm is very competitive

    Disparate In Vivo Efficacy of FTY720 in Xenograft Models of Philadelphia Positive and Negative B-lineage Acute Lymphoblastic Leukemia

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    Most patients with acute lymphoblastic leukemia (ALL) respond well to standard chemotherapy-based treatments. However a significant proportion of patients, particularly adult patients, relapse with the majority dying of leukemia. FTY720 is an immunosuppressive drug that was recently approved for the treatment of multiple sclerosis and is currently under pre-clinical investigation as a therapy for a number of hematological malignancies. Using human ALL xenografts in NOD/SCIDγc−/− mice, we show for the first time that three Ph+ human ALL xenografts responded to FTY720 with an 80±12% (p = 0.048) reduction in overall disease when treatment was commenced early. In contrast, treatment of mice with FTY720 did not result in reduced leukemia compared to controls using four separate human Ph− ALL xenografts. Although FTY720 reactivated PP2A in vitro, this reactivation was not required for death of Ph− ALL cells. The plasma levels of FTY720 achieved in the mice were in the high nanomolar range. However, the response seen in the Ph+ ALL xenografts when treatment was initiated early implies that in vivo efficacy may be obtained with substantially lower drug concentrations than those required in vitro. Our data suggest that while FTY720 may have potential as a treatment for Ph+ ALL it will not be a useful agent for the treatment of Ph− B-ALL

    The effects of violence and aggression from parents on child protection workers' personal, family and professional lives

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    Creative Commons CC-BY: This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).This article presents findings from a survey of the experiences of child protection workers in England when working with parents who exhibit aggression and violence. This work explores the effects on workers in their professional lives, and on themselves and their families in their private lives. The article examines workers’ thoughts and experiences about the effects of parental hostility on workers’ ability to protect children. The article also details workers’ experiences of the nature and effectiveness of training and support in this area. These findings are then examined in the light of the results of an analysis of the literature, including the findings from serious case review (SCR) reports in England (official inquiries into the causes of child deaths where the children are known to social and health services). The majority of the 590 respondents in the survey were social workers (n = 402; 68%), reflecting the fact that case management of child protection cases in the United Kingdom is the responsibility of social workers working in statutory agencies. This article addresses, from a consideration of the secondary analysis and the original research findings from the survey, how individual workers, managers, and agencies can best understand and then respond effectively to aggressive parental behaviors.Peer reviewe

    A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings

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    Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation).In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented.We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes

    A pilot study on mindfulness based stress reduction for smokers

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    BACKGROUND: Mindfulness means paying attention in the present moment, non-judgmentally, without commentary or decision-making. We report results of a pilot study designed to test the feasibility of using Mindfulness Based Stress Reduction (MBSR) (with minor modifications) as a smoking intervention. METHODS: MBSR instructors provided instructions in mindfulness in eight weekly group sessions. Subjects attempted smoking cessation during week seven without pharmacotherapy. Smoking abstinence was tested six weeks after the smoking quit day with carbon monoxide breath test and 7-day smoking calendars. Questionnaires were administered to evaluate changes in stress and affective distress. RESULTS: 18 subjects enrolled in the intervention with an average smoking history of 19.9 cigarettes per day for 26.4 years. At the 6-week post-quit visit, 10 of 18 subjects (56%) achieved biologically confirmed 7-day point-prevalent smoking abstinence. Compliance with meditation was positively associated with smoking abstinence and decreases in stress and affective distress. DISCUSSIONS AND CONCLUSION: The results of this study suggest that mindfulness training may show promise for smoking cessation and warrants additional study in a larger comparative trial

    "You have to get wet to learn how to swim" applied to bridging the gap between research into personnel scheduling and its implementation in practice

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    Personnel scheduling problems have attracted research interests for several decades. They have been considerably changed over time, accommodating a variety of constraints related to legal and organisation requirements, part-time staff, flexible hours of staff, staff preferences, etc. This led to a myriad of approaches developed for solving personnel scheduling problems including optimisation, meta-heuristics, artificial intelligence, decision-support, and also hybrids of these approaches. However, this still does not imply that this research has a large impact on practice and that state-of-the art models and algorithms are widely in use in organisations. One can find a reasonably large number of software packages that aim to assist in personnel scheduling. A classification of this software based on its purpose will be proposed, accompanied with a discussion about the level of support that this software offers to schedulers. A general conclusion is that the available software, with some exceptions, does not benefit from the wealth of developed models and methods. The remaining of the paper will provide insights into some characteristics of real-world scheduling problems that, in the author’s opinion, have not been given a due attention in the personnel scheduling research community yet and which could contribute to the enhancement of the implementation of research results in practice. Concluding remarks are that in order to bridge the gap that still exists between research into personnel scheduling and practice, we need to engage more with schedulers in practice and also with software developers; one may say we need to get wet if we want to learn how to swim

    Reproductive health for refugees by refugees in Guinea III: maternal health

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    BACKGROUND: Maternal mortality can be particularly high in conflict and chronic emergency settings, partly due to inaccessible maternal care. This paper examines associations of refugee-led health education, formal education, age, and parity on maternal knowledge, attitudes, and practices among reproductive-age women in refugee camps in Guinea. METHODS: Data comes from a 1999 cross-sectional survey of 444 female refugees in 23 camps. Associations of reported maternal health outcomes with exposure to health education (exposed versus unexposed), formal education (none versus some), age (adolescent versus adult), or parity (nulliparous, parous, grand multiparous), were analysed using logistic regression. RESULTS: No significant differences were found in maternal knowledge or attitudes. Virtually all respondents said pregnant women should attend antenatal care and knew the importance of tetanus vaccination. Most recognised abdominal pain (75%) and headaches (24%) as maternal danger signs and recommended facility attendance for danger signs. Most had last delivered at a facility (67%), mainly for safety reasons (99%). Higher odds of facility delivery were found for those exposed to RHG health education (adjusted odds ratio 2.03, 95%CI 1.23-3.01), formally educated (adjusted OR 1.93, 95%CI 1.05-3.92), or grand multipara (adjusted OR 2.13, 95%CI 1.21-3.75). Main reasons for delivering at home were distance to a facility (94%) and privacy (55%). CONCLUSIONS: Refugee-led maternal health education appeared to increase facility delivery for these refugee women. Improved knowledge of danger signs and the importance of skilled birth attendance, while vital, may be less important in chronic emergency settings than improving facility access where quality of care is acceptable

    The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma

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    Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM
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