The First Three Rungs of the Cosmological Distance Ladder

It is straightforward to determine the size of the Earth and the distance to the Moon without making use of a telescope. The methods have been known since the 3rd century BC. However, few amateur or professional astronomers have worked this out from data they themselves have taken. Here we use a gnomon to determine the latitude and longitude of South Bend, Indiana, and College Station, Texas, and determine a value of the radius of the Earth of 6290 km, only 1.4 percent smaller than the true value. We use the method of Aristarchus and the size of the Earth's shadow during the lunar eclipse of 2011 June 15 to derive an estimate of the distance to the Moon (62.3 R_Earth), some 3.3 percent greater than the true mean value. We use measurements of the angular motion of the Moon against the background stars over the course of two nights, using a simple cross staff device, to estimate the Moon's distance at perigee and apogee. Finally, we use simultaneous CCD observations of asteroid 1996 HW1 obtained with small telescopes in Socorro, New Mexico, and Ojai, California, to derive a value of the Astronomical Unit of (1.59 +/- 0.19) X 10^8 km, about 6 percent too large. The data and methods presented here can easily become part of a beginning astronomy lab class.Comment: 34 pages, 11 figures, accepted for publication in American Journal of Physic

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting

Background Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort‐ with nausea/vomiting‐predominant disease. Methods Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate‐severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [ PAGI ‐ SYM ] score ≥3) vs none‐mild ( PAGI ‐ SYM  < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. Key Results Upper abdominal pain was moderate‐severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate‐severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate‐severe pain (P ≤ 0.008). Factors associated with moderate‐severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. Conclusions & Inferences Moderate‐severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97520/1/nmo12091.pd

Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing

BackgroundEarly satiety (ES) and postprandial fullness (PPF) are often present in gastroparesis, but the importance of these symptoms in gastroparesis has not been well‐described. The aims were: (i) Characterize ES and PPF in patients with gastroparesis. (ii) Assess relationships of ES and PPF with etiology of gastroparesis, quality of life, body weight, gastric emptying, and water load testing.MethodsGastroparetic patients filled out questionnaires assessing symptoms (PAGI‐SYM) and quality of life (PAGI‐QOL, SF‐36v2). Patients underwent gastric emptying scintigraphy and water load testing.Key Results198 patients with gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic gastroparesis. Increasing severity of ES and PPF were associated with other gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing gastroparesis severity, decreased BMI, decreased quality of life from PAGI‐QOL and SF‐36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test.Conclusions & InferencesEarly satiety and PPF are commonly severe symptoms in both diabetic and idiopathic gastroparesis. Early satiety and PPF severity are associated with other gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136370/1/nmo12981_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136370/2/nmo12981.pd

Treatment of gastroparesis: a multidisciplinary clinical review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75594/1/j.1365-2982.2006.00760.x.pd

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimer\u2019s disease and type II diabetes, identified a tripyridylamide, ADH-6, that abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53\u2019s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment effectively shrinks xenografts harboring mutant p53, while exhibiting no toxicity to healthy tissue, thereby substantially prolonging survival. This study demonstrates the successful application of a bona fide small-molecule amyloid inhibitor as a potent\ua0anticancer agent