Revisiting performance persistence in real estate funds

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2005.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (leaves 46-47).In this thesis, real estate opportunity fund returns were analyzed for evidence of persistence in subsequent funds from the same manager; it is designed to update and enhance a prior thesis performed by Cathy C. Hahn (2003), using both parametric and non-parametric tests. Tests were performed on gross and net returns covering the period from 1991-2004. These tests confirm the prior finding that past fund performance is a significant indicator of future fund performance within the same firm. Our study also found the strongest evidence of persistence to exist in the extreme performers ranking in the top and bottom quartile amongst their vintage year peers. Additional tests for persistence, as well as effects of fund characteristics on performance, were employed using a methodology similar to that performed on private equity funds by Kaplan and Schoar (2003). Our tests yielded similar results to those found by Kaplan and Schoar(2003), but were not substantiated with statistical significance.by Robert A. LaFever and Luis Canizo.S.M

Living myocardial slices for the study of nucleic acid-based therapies

Gene therapy based on viral vectors offers great potential for the study and the treatment of cardiac diseases. Here we explore the use of Living Myocardial Slices (LMS) as a platform for nucleic acid-based therapies. Rat LMS and Adeno-Associated viruses (AAV) were used to optimise and analyse gene transfer efficiency, viability, tissue functionality, and cell tropism in cardiac tissue. Human cardiac tissue from failing (dilated cardiomyopathy) hearts was also used to validate the model in a more translational setting. LMS were cultured at physiological sarcomere length for 72-h under electrical stimulation. Two recombinant AAV serotypes (AAV6 and AAV9) at different multiplicity of infection (MOI) expressing enhanced green fluorescent protein (eGFP) were added to the surface of rat LMS. AAV6 at 20,000 MOI proved to be the most suitable serotype without affecting LMS contractility or kinetics and showing high transduction and penetrability efficiency in rat LMS. This serotype exhibited 40% of transduction efficiency in cardiomyocytes and stromal cells while 20% of the endothelial cells were transduced. With great translational relevance, this protocol introduces the use of LMS as a model for nucleic acid-based therapies, allowing the acceleration of preclinical studies for cardiac diseases

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course

Bone Marrow Mesenchymal Stem Cells for Improving Hematopoietic Function: An In Vitro and In Vivo Model. Part 2: Effect on Bone Marrow Microenvironment

The aim of the present study was to determine how mesenchymal stem cells (MSC) could improve bone marrow (BM) stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34+ progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC) were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin,) involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (IV) or intrabone (IB) route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Business analytics in industry 4.0: a systematic review

Recently, the term “Industry 4.0” has emerged to characterize several Information Technology and Communication (ICT) adoptions in production processes (e.g., Internet-of-Things, implementation of digital production support information technologies). Business Analytics is often used within the Industry 4.0, thus incorporating its data intelligence (e.g., statistical analysis, predictive modelling, optimization) expert system component. In this paper, we perform a Systematic Literature Review (SLR) on the usage of Business Analytics within the Industry 4.0 concept, covering a selection of 169 papers obtained from six major scientific publication sources from 2010 to March 2020. The selected papers were first classified in three major types, namely, Practical Application, Reviews and Framework Proposal. Then, we analysed with more detail the practical application studies which were further divided into three main categories of the Gartner analytical maturity model, Descriptive Analytics, Predictive Analytics and Prescriptive Analytics. In particular, we characterized the distinct analytics studies in terms of the industry application and data context used, impact (in terms of their Technology Readiness Level) and selected data modelling method. Our SLR analysis provides a mapping of how data-based Industry 4.0 expert systems are currently used, disclosing also research gaps and future research opportunities.The work of P. Cortez was supported by FCT - Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020. We would like to thank to the three anonymous reviewers for their helpful suggestions

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Local Current Distribution and Electrical Properties of a Magnetic Tunnel Junction Using Conducting Atomic Force Microscopy

[[abstract]]Local topographical and electrical properties were simultaneously measured for a magnetic tunnel junction formed by Ta (50 �)/Ni-Fe (20 �)/Cu (50 �)/Mn75 Ir25 (100 �)/Co70Fe30(40 �)/Al-O (8-15 �)/Co70Fe30 (40 �)/Ni-Fe (100 �)/Ta (50 �). Local current-voltage (I-V) characteristic curves were obtained for different contrast levels in the electrical current distribution images on the test sample. With the purpose of obtaining quantitative values for the barrier characteristics, data was analyzed by the Simmons' equation from -1.0 to 1.0 V. The magnetoresistance ratio values were estimated to be 35.02%, with a bias voltage of 0.36 V, when applying a magnetic field of �200 Oe. In addition, a study on the ramping effect on the dielectric tunneling capacitance and analytical resistance-capacitance (RC) model were carried out