273 research outputs found

    Forecasting and Automating Accurate Levels of Reserve for Contra Revenue, Using Artificial Intelligence

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    The process of balance sheet forecasting from the Contra revenue team, within HP Inc, is currently a manual process that takes a lot of manual work to make, currently only two forecasts are provided, one per business, and the scope needs to be expanded to the market level organizations in the company. The main objectives are to improve the forecast, to expand the scope and to automatize the process. The solution is a friendly executable that uses Python and an ARIMA algorithm to provide the next value of reserve entering an Excel file with organized data, that goes through the algorithm, and exiting an Excel file for the analyst to keep working on their own deliverable

    PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection.

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    Cohesin is a chromatin-bound complex that mediates sister chromatid cohesion and facilitates long-range interactions through DNA looping. How the transcription and replication machineries deal with the presence of cohesin on chromatin remains unclear. The dynamic association of cohesin with chromatin depends on WAPL cohesin release factor (WAPL) and on PDS5 cohesin-associated factor (PDS5), which exists in two versions in vertebrate cells, PDS5A and PDS5B. Using genetic deletion in mouse embryo fibroblasts and a combination of CRISPR-mediated gene editing and RNAi-mediated gene silencing in human cells, here we analyzed the consequences of PDS5 depletion for DNA replication. We found that either PDS5A or PDS5B is sufficient for proper cohesin dynamics and that their simultaneous removal increases cohesin's residence time on chromatin and slows down DNA replication. A similar phenotype was observed in WAPL-depleted cells. Cohesin down-regulation restored normal replication fork rates in PDS5-deficient cells, suggesting that chromatin-bound cohesin hinders the advance of the replisome. We further show that PDS5 proteins are required to recruit WRN helicase-interacting protein 1 (WRNIP1), RAD51 recombinase (RAD51), and BRCA2 DNA repair associated (BRCA2) to stalled forks and that in their absence, nascent DNA strands at unprotected forks are degraded by MRE11 homolog double-strand break repair nuclease (MRE11). These findings indicate that PDS5 proteins participate in replication fork protection and also provide insights into how cohesin and its regulators contribute to the response to replication stress, a common feature of cancer cells.This work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER Grants BFU2013-48481-R and BFU2016-79841-R (to A. L.) and BFU2016-80402-R (to J. M.) and by FPI "Severo Ochoa" fellowships (to C. M. and M. R.-T.). This work was also supported by funding from Boehringer Ingelheim Fonds (to M. R.-T.). The authors declare that they have no conflicts of interest with the contents of this article.S

    Using a stakeholder-engaged, iterative, and systematic approach to adapting collaborative decision skills training for implementation in VA psychosocial rehabilitation and recovery centers

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    Background: Adaptation of interventions is inevitable during translation to new populations or settings. Systematic approach to adaptation can ensure that fidelity to core functions of the intervention are preserved while optimizing implementation feasibility and effectiveness for the local context. In this study, we used an iterative, mixed methods, and stakeholder-engaged process to systematically adapt Collaborative Decision Skills Training for Veterans with psychosis currently participating in VA Psychosocial Rehabilitation and Recovery Centers. Methods: A modified approach to Intervention Mapping (IM-Adapt) guided the adaptation process. An Adaptation Resource Team of five Veterans, two VA clinicians, and four researchers was formed. The Adaptation Resource Team engaged in an iterative process of identifying and completing adaptations including individual qualitative interviews, group meetings, and post-meeting surveys. Qualitative interviews were analyzed using rapid matrix analysis. We used the modified, RE-AIM enriched expanded Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME) to document adaptations. Additional constructs included adaptation size and scope; implementation of planned adaptation (yes–no); rationale for non-implementation; and tailoring of adaptation for a specific population (e.g., Veterans). Results: Rapid matrix analysis of individual qualitative interviews resulted in 510 qualitative codes. Veterans and clinicians reported that the intervention was a generally good ft for VA Psychosocial Rehabilitation and Recovery Centers and for Veterans. Following group meetings to reach adaptation consensus, 158 adaptations were completed. Most commonly, adaptations added or extended a component; were small in size and scope; intended to improve the effectiveness of the intervention, and based on experience as a patient or working with patients. Few adaptations were targeted towards a specific group, including Veterans. Veteran and clinician stakeholders reported that these adaptations were important and would benefit Veterans, and that they felt heard and understood during the adaptation process. Conclusions: A stakeholder-engaged, iterative, and mixed methods approach was successful for adapting Collaborative Decision Skills Training for immediate clinical application to Veterans in a psychosocial rehabilitation center. The ongoing interactions among multiple stakeholders resulted in high quality, tailored adaptations which are likely to be generalizable to other populations or settings. We recommend the use of this stakeholder-engaged, iterative approach to guide adaptations

    Postural directionality and head tremor in cervical dystonia

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    Background: Although abnormal head and neck postures are defining features of cervical dystonia (CD), head tremor (HT) is also common. However, little is known about the relationship between abnormal postures and HT in CD. Methods: We analyzed clinical data and video recordings from 185 patients enrolled by the Dystonia Coalition. We calculated the likelihood of their HT and HT type ( regular vs. jerky ) given directionality of abnormal head postures, disease duration, sex, and age. Results: Patients with retrocollis were more likely to have HT than patients with anterocollis (X Discussion: We found that HT is more likely for CD patients with a specific directionality in their predominant posture. Our finding that CD patients with longer disease duration have a higher likelihood of HT also raises the question of whether HT becomes more likely over time in individual patients

    Interrater reliability of motor severity scales for hemifacial spasm

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    To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants\u27 motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee\u27s scale), clinical grading of spasm intensity (Chen\u27s scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc\u27s scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from poor to moderate ; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee\u27s, Chen\u27s, and Tunc\u27s scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc\u27s scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc\u27s scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training

    External validation of the INCREMENT-CPE mortality score in a carbapenem-resistant Klebsiella pneumoniae bacteraemia cohort: the prognostic significance of colistin resistance

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    External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68–0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69–3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55–3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73–4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.This study was supported by Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001; RD16/0016/0008], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative Program Intelligent Growth 2014–2020
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