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Institution

Eli Lilly and Company

CompanyIndianapolis, Indiana, United States
About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.
Topics: Population, Agonist, Insulin, Placebo, Olanzapine


Papers
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Journal ArticleDOI
TL;DR: It is reported that TREM2 protects mice from Alzheimer's disease by enabling resident microglia to insulate and alter Aβ plaque structure, thereby limiting neuritic damage.
Abstract: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor that recognizes changes in the lipid microenvironment, which may occur during amyloid β (Aβ) accumulation and neuronal degeneration in Alzheimer's disease (AD). Rare TREM2 variants that affect TREM2 function lead to an increased risk of developing AD. In murine models of AD, TREM2 deficiency prevents microglial clustering around Aβ deposits. However, the origin of myeloid cells surrounding amyloid and the impact of TREM2 on Aβ accumulation are a matter of debate. Using parabiosis, we found that amyloid-associated myeloid cells derive from brain-resident microglia rather than from recruitment of peripheral blood monocytes. To determine the impact of TREM2 deficiency on Aβ accumulation, we examined Aβ plaques in the 5XFAD model of AD at the onset of Aβ-related pathology. At this early time point, Aβ accumulation was similar in TREM2-deficient and -sufficient 5XFAD mice. However, in the absence of TREM2, Aβ plaques were not fully enclosed by microglia; they were more diffuse, less dense, and were associated with significantly greater neuritic damage. Thus, TREM2 protects from AD by enabling microglia to surround and alter Aβ plaque structure, thereby limiting neuritic damage.

534 citations

Journal ArticleDOI
TL;DR: The pathogenic effects of the dimeric Aβ-(1-40/42) were tested in cultures of rat hippocampal neuron glia cells and only in the presence of microglia did the dimer elicit neuronal killing.

534 citations

Journal ArticleDOI
03 Nov 2015-Trials
TL;DR: There is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions, by modifying trial design modification to include a more representative patient sample and supplementing RCT evidence with data generated from observational studies.
Abstract: Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner.

532 citations

Journal ArticleDOI
TL;DR: The pilot Adult ADHD Self-Report Scale symptom checklist is a reliable and valid scale for evaluating ADHD for adults and shows a high internal consistency and high concurrent validity with the rater-administered ADHD RS.
Abstract: Background. The goal of this study was to validate the pilot Adult ADHD Self-Report Scale (pilot ASRS) versus standard clinician ratings on the ADHD Rating Scale (ADHD RS).Method. Sixty adult ADHD patients took the self-administered ADHD RS and then raters administered the standard ADHD RS. Internal consistency of symptom scores was assessed by Cronbach's alpha. Agreement of raters was established by intra-class correlation coefficients (ICCs) between scales.Results. Internal consistency was high for both patient and rater-administered versions (Cronbach's alpha 0.88, 0.89, respectively). The ICC between scales for total scores was also high (0.84); ICCs for subset symptom scores were also high (both 0.83). There was acceptable agreement for individual items (% agreement: 43%–72%) and significant kappa coefficients for all items (p < 0.001).Conclusions. The pilot Adult ADHD Self-Report Scale symptom checklist is a reliable and valid scale for evaluating ADHD for adults and shows a high internal consistenc...

530 citations


Authors

Showing all 17866 results

NameH-indexPapersCitations
Mark J. Daly204763304452
Irving L. Weissman2011141172504
Eric J. Topol1931373151025
Tony Hunter175593124726
Xiang Zhang1541733117576
Jerrold M. Olefsky14359577356
Stephen F. Badylak13353057083
George A. Bray131896100975
Lloyd Paul Aiello13150685550
Levi A. Garraway12936699989
Mark Sullivan12680263916
James A. Russell124102487929
Tony L. Yaksh12380660898
Elisabetta Dejana12243048254
Hagop S. Akiskal11856550869
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20236
202287
2021815
2020868
2019732
2018742