Maximum likelihood analysis of balanced incomplete block models

Maximum likelihood analysis of balanced incomplete blocks, and amall-sample properties of maximum likelihood estimate

The CTRW in finance: Direct and inverse problems with some generalizations and extensions

We study financial distributions within the framework of the continuous time random walk (CTRW). We review earlier approaches and present new results related to overnight effects as well as the generalization of the formalism which embodies a non-Markovian formulation of the CTRW aimed to account for correlated increments of the return.Comment: 25 pages, 3 figures, Elsart, submitted for publicatio

Simplified production and concentration of HIV-1-based lentiviral vectors using HYPERFlask vessels and anion exchange membrane chromatography

<p>Abstract</p> <p>Background</p> <p>During the past twelve years, lentiviral (LV) vectors have emerged as valuable tools for transgene delivery because of their ability to transduce nondividing cells and their capacity to sustain long-term transgene expression in target cells <it>in vitro </it>and <it>in vivo</it>. However, despite significant progress, the production and concentration of high-titer, high-quality LV vector stocks is still cumbersome and costly.</p> <p>Methods</p> <p>Here we present a simplified protocol for LV vector production on a laboratory scale using HYPERFlask vessels. HYPERFlask vessels are high-yield, high-performance flasks that utilize a multilayered gas permeable growth surface for efficient gas exchange, allowing convenient production of high-titer LV vectors. For subsequent concentration of LV vector stocks produced in this way, we describe a facile protocol involving Mustang Q anion exchange membrane chromatography.</p> <p>Results</p> <p>Our results show that unconcentrated LV vector stocks with titers in excess of 10⁸transduction units (TU) per ml were obtained using HYPERFlasks and that these titers were higher than those produced in parallel using regular 150-cm²tissue culture dishes. We also show that up to 500 ml of an unconcentrated LV vector stock prepared using a HYPERFlask vessel could be concentrated using a single Mustang Q Acrodisc with a membrane volume of 0.18 ml. Up to 5.3 × 10¹⁰TU were recovered from a single HYPERFlask vessel.</p> <p>Conclusion</p> <p>The protocol described here is easy to implement and should facilitate high-titer LV vector production for preclinical studies in animal models without the need for multiple tissue culture dishes and ultracentrifugation-based concentration protocols.</p

Palliative care and Parkinson's disease : meeting summary and recommendations for clinical research

Introduction: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson’s disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. Methods: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson’s Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. Results: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. Conclusions: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers

A continuous time random walk model for financial distributions

We apply the formalism of the continuous time random walk to the study of financial data. The entire distribution of prices can be obtained once two auxiliary densities are known. These are the probability densities for the pausing time between successive jumps and the corresponding probability density for the magnitude of a jump. We have applied the formalism to data on the US dollar/Deutsche Mark future exchange, finding good agreement between theory and the observed data.Comment: 14 pages, 5 figures, revtex4, submitted for publicatio

Cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from Sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus

<p>Abstract</p> <p>Background</p> <p>The ability to efficiently and selectively target gene delivery vectors to specific cell types <it>in vitro </it>and <it>in vivo </it>remains one of the formidable challenges in gene therapy. We pursued two different strategies to target lentiviral vector delivery to specific cell types. In one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on Sindbis virus strain TR339 glycoproteins or the vesicular stomatitis virus G glycoprotein were used to selectively transduce cells expressing the corresponding stem cell factor receptor (c-kit). An alternative approach involved soluble avian sarcoma/leukosis virus receptors fused to cell-specific ligands including stem cell factor and erythropoietin for targeting lentiviral vectors pseudotyped with avian sarcoma/leukosis virus envelope proteins to cells that express the corresponding receptors.</p> <p>Results</p> <p>The titers of unconcentrated vector particles bearing Sindbis virus strain TR339 or vesicular stomatitis virus G fusion proteins plus stem cell factor in the context of c-kit expressing cells were up to 3.2 × 10⁵transducing units per ml while vector particles lacking the stem cell factor ligand displayed titers that were approximately 80 fold lower. On cells that lacked the c-kit receptor, the titers of stem cell factor-containing vectors were approximately 40 times lower compared to c-kit-expressing cells.</p> <p>Lentiviral vectors pseudotyped with avian sarcoma/leukosis virus subgroup A or B envelope proteins and bearing bi-functional bridge proteins encoding erythropoietin or stem cell factor fused to the soluble extracellular domains of the avian sarcoma/leukosis virus subgroup A or B receptors resulted in efficient transduction of erythropoietin receptor or c-kit-expressing cells. Transduction of erythropoietin receptor-expressing cells mediated by bi-functional bridge proteins was found to be dependent on the dose, the correct subgroup-specific virus receptor and the correct envelope protein. Furthermore, transduction was completely abolished in the presence of anti-erythropoietin antibody.</p> <p>Conclusions</p> <p>Our results indicate that the avian sarcoma/leukosis virus bridge strategy provides a reliable approach for cell-specific lentiviral vector targeting. The background levels were lower compared to alternative strategies involving Sindbis virus strain TR339 or vesicular stomatitis virus fusion proteins.</p

Adherence to

(MWM) for palliative care has prioritized data collection efforts for evaluating quality in clinical practice. How these measures can be implemented across diverse clinical settings using point-of-care data collection on quality is unknown.To evaluate the implementation of MWM measures by exploring documentation of quality measure adherence across six diverse clinical settings inherent to palliative care practice.We deployed a point-of-care quality data collection system, the Quality Data Collection Tool, across five organizations within the Palliative Care Research Cooperative Group. Quality measures were recorded by clinicians or assistants near care delivery.During the study period, 1989 first visits were included for analysis. Our population was mostly white, female, and with moderate performance status. About half of consultations were seen on hospital general floors. We observed a wide range of adherence. The lowest adherence involved comprehensive assessments during the first visit in hospitalized patients in the intensive care unit (2.71%); the highest adherence across all settings, with an implementation of >95%, involved documentation of management of moderate/severe pain. We observed differences in adherence across clinical settings especially with MWM Measure #2 (Screening for Physical Symptoms, range 45.7%–81.8%); MWM Measure #5 (Discussion of Emotional Needs, range 46.1%–96.1%); and MWM Measure #6 (Documentation of Spiritual/Religious Concerns, range 0–69.6%).Variations in clinician documentation of adherence to MWM quality measures are seen across clinical settings. Additional studies are needed to better understand benchmarks and acceptable ranges for adherence tailored to various clinical settings

Study of Digital Competence of the Students and Teachers in Ukraine

Professional fulfillment of the personality at the conditions of the digital economy requires the high level of digital competency. One of the ways to develop these competencies is education. However, to provide the implementation of digital education at a high level, the digital competency of the teachers and students is a must. This paper presents explanations on the level determination of the digital competencies for teachers and students in Ukraine according to the DigComp recommendations. We tried to identify the main factors that reflect the degree of readiness teachers and students for digital education based on their self-evaluation. We also attempted to estimate the level of digital competencies based on the analysis of Case-Studies execution results. The complex analysis let us assess the connection between respondents’ self-evaluation and their real competencies. Here we provide a methodology and a model of level competencies determination by means of a survey, expert case rating and the results of the statistical analysis. On the basis of the obtained results, this paper suggests further research prospects and recommendations on the digital competency development in educational institutions in Ukraine