Pseudorehearsal in value function approximation

Catastrophic forgetting is of special importance in reinforcement learning, as the data distribution is generally non-stationary over time. We study and compare several pseudorehearsal approaches for Q-learning with function approximation in a pole balancing task. We have found that pseudorehearsal seems to assist learning even in such very simple problems, given proper initialization of the rehearsal parameters

Moderation in management research: What, why, when and how.

Many theories in management, psychology, and other disciplines rely on moderating variables: those which affect the strength or nature of the relationship between two other variables. Despite the near-ubiquitous nature of such effects, the methods for testing and interpreting them are not always well understood. This article introduces the concept of moderation and describes how moderator effects are tested and interpreted for a series of model types, beginning with straightforward two-way interactions with Normal outcomes, moving to three-way and curvilinear interactions, and then to models with non-Normal outcomes including binary logistic regression and Poisson regression. In particular, methods of interpreting and probing these latter model types, such as simple slope analysis and slope difference tests, are described. It then gives answers to twelve frequently asked questions about testing and interpreting moderator effects

Microarray studies reveal novel genes associated with endocrine resistance in breast cancer

Background Endocrine resistance is a major hurdle in breast cancer management, and determining the underlying factors driving its growth and aggressive behaviour should vastly improve treatment. Methods Microarray technology (BD Atlas Plastic Human 12 K Microarrays; GeneSifter software), verified by PCR, western blotting and immunocytochemisty, was used to identify genes increased in acquired resistant models to tamoxifen (TamR) or faslodex (FasR) as potential predictive/prognostic markers and new therapeutic targets. Results Alongside known breast cancer genes (β-catenin, PEA3, vitronectin, CD44), two novel genes in endocrine resistance were revealed (the latter never previously described in breast cancer): a securin/cell cycle regulator Pituitary Tumour Transforming Gene-1 (PTTG1), and GDNF receptor-alpha 3 (GFRα3) reported to promote cell survival signalling via RET coreceptor. Altered levels of PTTG1, GFRα3, or their associated family members were observed in further endocrine resistant states, including an additional faslodex resistant model that has progressed to a highly-aggressive state (FasR-Lt) and XMCF-7 cells resistant to oestrogen deprivation. PTTG1 and GFRα3 induction were also implicated in limiting response to anti-EGFR agents currently in breast cancer trials, with GFRα3 ligand (artemin) largely overcoming drug response. mRNA studies in clinical disease revealed PTTG1 associated with lymph node spread, high tumour grade and proliferation, while GFRα3 was enriched in ER-negative tumours and those expressing EGFR, profiles implying roles in clinical resistance and aggressive tumour behaviour. Promisingly, PTTG1 or GFRα3 siRNA knockdown promoted cell kill and inhibited proliferation in the resistant models. Conclusion Cumulatively, these data indicate PTTG1 and GFRα3 may provide useful biomarkers, and perhaps clinically relevant therapeutic targets for multiple resistant states

Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators

Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods. Methods: Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth. Results: Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status. Conclusions: Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials. © 2011 Dezzutti et al

Evaluation of emergency department performance:A systematic review on recommended performance and quality-in-care measures

BACKGROUND: Evaluation of emergency department (ED) performance remains a difficult task due to the lack of consensus on performance measures that reflects high quality, efficiency, and sustainability. AIM: To describe, map, and critically evaluate which performance measures that the published literature regard as being most relevant in assessing overall ED performance. METHODS: Following the PRISMA guidelines, a systematic literature review of review articles reporting accentuated ED performance measures was conducted in the databases of PubMed, Cochrane Library, and Web of Science. Study eligibility criteria includes: 1) the main purpose was to discuss, analyse, or promote performance measures best reflecting ED performance, 2) the article was a review article, and 3) the article reported macro-level performance measures, thus reflecting an overall departmental performance level. RESULTS: A number of articles addresses this study’s objective (n = 14 of 46 unique hits). Time intervals and patient-related measures were dominant in the identified performance measures in review articles from US, UK, Sweden and Canada. Length of stay (LOS), time between patient arrival to initial clinical assessment, and time between patient arrivals to admission were highlighted by the majority of articles. Concurrently, “patients left without being seen” (LWBS), unplanned re-attendance within a maximum of 72 hours, mortality/morbidity, and number of unintended incidents were the most highlighted performance measures that related directly to the patient. Performance measures related to employees were only stated in two of the 14 included articles. CONCLUSIONS: A total of 55 ED performance measures were identified. ED time intervals were the most recommended performance measures followed by patient centeredness and safety performance measures. ED employee related performance measures were rarely mentioned in the investigated literature. The study’s results allow for advancement towards improved performance measurement and standardised assessment across EDs

Supportive and symptomatic management of amyotrophic lateral sclerosis

The main aims in the care of individuals with amyotrophic lateral sclerosis (ALS) are to minimize morbidity and maximize quality of life. Although no cure exists for ALS, supportive and symptomatic care provided by a specialist multidisciplinary team can improve survival. The basis for supportive management is shifting from expert consensus guidelines towards an evidence-based approach, which encourages the use of effective treatments and could reduce the risk of harm caused by ineffective or unsafe interventions. For example, respiratory support using noninvasive ventilation has been demonstrated to improve survival and quality of life, whereas evidence supporting other respiratory interventions is insufficient. Increasing evidence implicates a causal role for metabolic dysfunction in ALS, suggesting that optimizing nutrition could improve quality of life and survival. The high incidence of cognitive dysfunction and its impact on prognosis is increasingly recognized, although evidence for effective treatments is lacking. A variety of strategies are used to manage the other physical and psychological symptoms, the majority of which have yet to be thoroughly evaluated. The need for specialist palliative care throughout the disease is increasingly recognized. This Review describes the current approaches to symptomatic and supportive care in ALS and outlines the current guidance and evidence for these strategies

Valorizing the Human Capital Within Organizations : A Competency Based Approach

Changes in the business environment and in the nature of work itself require the implementation of integrated and flexible methodologies in competencies’ definition in order to valorize the human capital and achieve organizational targets in a future-oriented perspective. However, extant research suggests that the available approaches to competency definition are more focused on describing past behaviors than on anticipating future requirements. Therefore, this study endeavors to provide a competency-based model that supports the top management in the identification of the competencies employees should posses, highlighting crucial competencies that can translate the strategy and vision of the organization into behaviors, skills, and terms that people can easily understand and implement. The results of our explorative case study led us to identify a set of competencies (digital/analytical/technical/adaptive/combinative/proactive), classified following the Knowledge Skills Attitudes (KSA) model, that collectively lead to a successful definition of future-oriented competencies.© 2019 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Society. AHFE 2018. The final authenticated version is available online at: https://doi.org/10.1007/978-3-319-94709-9_6fi=vertaisarvioitu|en=peerReviewed

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

Low serum albumin and the acute phase response predict low serum selenium in HIV-1 infected women

BACKGROUND: Low serum selenium has been associated with lower CD4 counts and greater mortality among HIV-1-seropositive individuals, but most studies have not controlled for serum albumin and the presence of an acute phase response. METHODS: A cross-sectional study was conducted to evaluate relationships between serum selenium concentrations and CD4 count, plasma viral load, serum albumin, and acute phase response markers among 400 HIV-1-seropositive women. RESULTS: In univariate analyses, lower CD4 count, higher plasma viral load, lower albumin, and the presence of an acute phase response were each significantly associated with lower serum selenium concentrations. In multivariate analyses including all four of these covariates, only albumin remained significantly associated with serum selenium. For each 0.1 g/dl increase in serum albumin, serum selenium increased by 0.8 μg/l (p < 0.001). Women with an acute phase response also had lower serum selenium (by 5.6 μg/l, p = 0.06). CONCLUSION: Serum selenium was independently associated with serum albumin, but not with CD4 count or plasma viral load, in HIV-1-seropositive women. Our findings suggest that associations between lower serum selenium, lower CD4 count, and higher plasma viral load may be related to the frequent occurrence of low serum albumin and the acute phase response among individuals with more advanced HIV-1 infection