Pneumococcal Immunization Reduces Neurological and Hepatic Symptoms in a Mouse Model for Niemann-Pick Type C1 Disease

Niemann-Pick type C1 (NPC1) disease is caused by a deleterious mutation in the Npc1 gene, causing lysosomal accumulation of unesterified cholesterol and sphingolipids. Consequently, NPC1 disease patients suffer from severe neurovisceral symptoms which, in the absence of effective treatments, result in premature death. NPC1 disease patients display increased plasma levels of cholesterol oxidation products such as those enriched in oxidized low-density lipoprotein (oxLDL), a pro-inflammatory mediator. While it has been shown that inflammation precedes and exacerbates symptom severity in NPC1 disease, it is unclear whether oxLDL contributes to NPC1 disease progression. In this study, we investigated the effects of increasing anti-oxLDL IgM autoantibodies on systemic and neurological symptoms in an NPC1 disease mouse model. For this purpose, Npc1 nih mice were immunized with heat-inactivated S. pneumoniae, an immunogen which elicits an IgM autoantibody-mediated immune response against oxLDL. Npc1 nih mice injected with heat-inactivated pneumococci displayed an improved hepatic phenotype, including liver lipid accumulation and inflammation. In addition, regression of motor skills was delayed in immunized Npc1 nih . In line with these results, brain analyses showed an improved cerebellar phenotype and neuroinflammation in comparison with control-treated subjects. This study highlights the potential of the pneumococcal immunization as a novel therapeutical approach in NPC1 disease. Future research should investigate whether implementation of this therapy can improve life span and quality of life of NPC1 disease patients

Family Involvement in Management and Product Innovation: The Mediating Role of R&D Strategies

Following calls to capture family firms’ innovative behavior and to specifically clarify how family firms manage product innovations to achieve sustainable economic development, this study empirically investigates the mediating role of Research & Development (R&D) strategies (i.e., intramural R&D investments, extramural R&D investments, and the combination of both intramural and extramural R&D investments) in the relationship between family involvement in the management and likelihood of obtaining product innovations. Carrying out a panel data analysis that is based on 7264 observations of Spanish manufacturing firms throughout the 2000–2015 period, our results suggest a negative effect of the level of family management on the likelihood of introducing product innovations. Moreover, we found that intramural R&D investments and the investment strategy consisting of both intramural and extramural R&D mediated the family involvement in management-likelihood of obtaining product innovations relationship. Our findings contribute important insights to the comprehension of which determinants instigate product innovation in family managed firms

Direct and cross-scheme effects in a research and development subsidy program

This study investigates the effects of an R&D subsidy scheme on participating firms’ net R&D investment. Making use of a specific policy design in Belgium that explicitly distinguishes between research and development grants, we estimate direct and cross-scheme effects on research versus development intensities in recipients firms. We find positive direct effects from research (development) subsidies on net research (development) spending. This direct effect is larger for research grants than for development grants. We also find cross-scheme effects that may arise due to complementarity between research and development activities. Finally, we find that the magnitude of the treatment effects depends on firm size and age and that there is a minimum effective grant size, especially for research projects. The results support the view that public subsidies induce higher additional investment particularly in research where market failures are larger, even when the subsidies are targeting development

Investigating rare haematological disorders - A celebration of 10 years of the Sherlock Holmes symposia

The Sherlock Holmes symposia have been educating haematologists on the need for prompt recognition, diagnosis and treatment of rare haematological diseases for 10 years. These symposia, which are supported by an unrestricted educational grant from Sanofi Genzyme, encourage haematologists to consider rare disorders in differential diagnoses. Improvement in rare disease awareness is important because diagnostics and the availability of effective therapies have improved considerably, meaning that rare haematological diseases can be accurately diagnosed and successfully managed, particularly if they are identified early. The Sherlock Holmes symposia programme includes real-life interactive clinical cases of rare haematological disorders that require awareness from the physician, to be diagnosed at an early stage. The audience are encouraged to examine each case as if they were detectives, look for clues from the clinical history and presentation, consider the potential causes, assess which tests would be required to make a definitive diagnosis and suggest optimal treatment options. To celebrate the 10-year anniversary of the Sherlock Holmes symposia, this article describes a number of clinical cases that include anaemia, thrombocytopaenia and splenomegaly among the presenting symptoms, to illustrate the importance of rigorous differential diagnosis in the identification of rare haematological disorders

Embry-Riddle Fly Paper 1943-01-15

https://commons.erau.edu/fly-paper/1159/thumbnail.jp

Business experience and start-up size: buying more lottery tickets next time around?

This paper explores the determinants of start-up size by focusing on a cohort of 6247 businesses that started trading in 2004, using a unique dataset on customer records at Barclays Bank. Quantile regressions show that prior business experience is significantly related with start-up size, as are a number of other variables such as age, education and bank account activity. Quantile treatment effects (QTE) estimates show similar results, with the effect of business experience on (log) start-up size being roughly constant across the quantiles. Prior personal business experience leads to an increase in expected start-up size of about 50%. Instrumental variable QTE estimates are even higher, although there are concerns about the validity of the instrument