Search

Author(s): W. M. Grundy (corresponding author) [1]; D. P. Cruikshank [2]; G. R. Gladstone [3]; C. J. A. Howett [4]; T. R. Lauer [5]; J. R. Spencer [4]; M. E. [...]

Patient reported outcomes (PROs) are becoming increasingly important in cancer studies, particularly with the emphasis on patient centered outcome research. However, multiple PROs, using different scales, with different directions of favorability are often used within a trial, making interpretation difficult. To enhance interpretability, we propose the use of a standardized effect size graph, which shows all PROs from a study on the same figure, on the same scale. Plotting standardized effects with their 95% confidence intervals (CIs) on a single graph clearly showing the null value conveys a comprehensive picture of trial results. We demonstrate how to create such a graph using data from a randomized controlled trial that measured 12 PROs at two time points. The 24 effect sizes and CIs are shown on one graph and clearly indicate that the intervention is effective and sustained. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the distribution and properties of 146 craters with impact melt deposits exterior to their rims. Many of these craters were only recently discovered due to their unusual radar properties in the near-global Mini-RF data set. We find that most craters with exterior deposits of impact melt are small, ⩽20km, and that the smallest craters have the longest melt flows relative to their size. In addition, exterior deposits of impact melt are more common in the highlands than the mare. This may be the result of differing target properties in the highlands and mare, the difference in titanium content, or the greater variation of topography in the highlands. We find that 80% of complex craters and 60% of simple craters have melt directions that are coincident or nearly coincident with the lowest point in their rim, implying that pre-existing topography plays a dominant role in melt emplacement. This is likely due to movement during crater modification (complex craters) or breached crater rims (simple craters). We also find that impact melt flows have very high circular polarization ratios compared to other features on the Moon. This suggests that their surfaces are some of the roughest material on the Moon at the centimeter to decimeter scale, even though they appear smooth at the meter scale. [ABSTRACT FROM AUTHOR]

Tidal interactions between planets or stars and the bodies that orbit them dissipate energy in their interiors. The dissipated energy heats the interior and a fraction of that energy will be released as seismic energy. Here we formalize a model to describe the tidally-driven seismic activity on planetary bodies based on tidal dissipation. To constrain the parameters of our model we use the seismic activity of the Moon, driven by tidal dissipation from the Earth-Moon interactions. We then apply this model to predict the amount of seismic energy release and largest seismic events on other moons in our Solar System and exoplanetary bodies. We find that many moons in the Solar System should be more seismically active than the Earth's Moon and many exoplanets should exhibit more seismic activity than the Earth. Finally, we examine how temporal-spatial variations in tidal dissipation manifest as variations in the locations and timing of seismic events on these bodies.

Objective: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer., Materials and Methods: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes., Results: EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001)., Conclusion: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We present the case for the presence of complex organic molecules, such as amino acids and nucleobases, formed by abiotic processes on the surface and in near-subsurface regions of Pluto. Pluto's surface is tinted with a range of non-ice substances with colors ranging from light yellow to red to dark brown; the colors match those of laboratory organic residues called tholins. Tholins are broadly characterized as complex, macromolecular organic solids consisting of a network of aromatic structures connected by aliphatic bridging units ( e.g., Imanaka et al., 2004; Materese et al., 2014, 2015). The synthesis of tholins in planetary atmospheres and in surface ices has been explored in numerous laboratory experiments, and both gas- and solid-phase varieties are found on Pluto. A third variety of tholins, exposed at a site of tectonic surface fracturing called Virgil Fossae, appears to have come from a reservoir in the subsurface. Eruptions of tholin-laden liquid H 2 O from a subsurface aqueous repository appear to have covered portions of Virgil Fossae and its surroundings with a uniquely colored deposit (D.P. Cruikshank, personal communication) that is geographically correlated with an exposure of H 2 O ice that includes spectroscopically detected NH 3 (C.M. Dalle Ore, personal communication). The subsurface organic material could have been derived from presolar or solar nebula processes, or might have formed in situ . Photolysis and radiolysis of a mixture of ices relevant to Pluto's surface composition (N 2 , CH 4 , CO) have produced strongly colored, complex organics with a significant aromatic content having a high degree of nitrogen substitution similar to the aromatic heterocycles pyrimidine and purine (Materese et al., 2014, 2015; Cruikshank et al., 2016). Experiments with pyrimidines and purines frozen in H 2 O-NH 3 ice resulted in the formation of numerous nucleobases, including the biologically relevant guanine, cytosine, adenine, uracil, and thymine (Materese et al., 2017). The red material associated with the H 2 O ice may contain nucleobases resulting from energetic processing on Pluto's surface or in the interior. Some other Kuiper Belt objects also exhibit red colors similar to those found on Pluto and may therefore carry similar inventories of complex organic materials. The widespread and ubiquitous nature of similarly complex organic materials observed in a variety of astronomical settings drives the need for additional laboratory and modeling efforts to explain the origin and evolution of organic molecules. Pluto observations reveal complex organics on a small body that remains close to its place of origin in the outermost regions of the Solar System.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU 69 , a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU 69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU 69 's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Still's disease is characterized by arthritis, fever, rash, lymphoid hypertrophy, leukocytosis, and anemia, often in association with thrombocytosis. We describe a patient with Still's disease and thrombocytopenia secondary to disseminated intravascular coagulation (DIC). Fifteen definite cases of DIC complicating Still's disease have been reported in the English literature. Most developed this complication while receiving high doses of salicylates in association with hepatic dysfunction. In a few, the coagulopathy has been associated with gold therapy. Our patient is only the second reported to develop DIC in the absence of drug therapy and the fourth reported to die from this complication. The clinical features of these 16 patients are summarized and proposed mechanisms of pathogenesis are reviewed.

Two patients developed drug induced lupus secondary to sulfasalazine (SSZ). One patient was receiving SSZ for Crohn's disease and was subsequently treated with olsalazine, which lacks the sulfapyridine component of SSZ. Her inflammatory bowel disease (IBD) remained controlled and she did not develop a recurrence of lupus, suggesting that olsalazine is safe in patients with IBD and a history of SSZ induced lupus. The SSZ induced antibodies were predominantly IgG against the (H2A-H2B)-DNA complex. Since lupus induced by 7 other drugs was associated with a similar antibody response, our findings support the existence of a common pathway for autoantibody induction.

An 18-year-old woman with thrombotic thrombocytopenic purpura (TTP) had recurrent thrombocytopenia due to antiplatelet antibodies associated with systemic lupus erythematosus (SLE). The simultaneous occurrence of TTP and SLE is rare. We briefly summarize eight previously reported cases in which these two diseases have developed in the same patient within a 12-month period. The possibility of a common pathogenesis is discussed.

Background: There have been many case reports of substantial renal disease in association with anticoagulation, yet the intensity of anticoagulation has changed over the years. In 1986, the American College of Chest Physicians and the Heart, Lung, and Blood Institute recommended a decrease in anticoagulation intensity. In addition, a variety of new methods to investigate hematuria have evolved, including computed tomography and red blood cell morphologic analysis. Because of these developments, we initiated a prospective study to evaluate the relationship between anticoagulation, microscopic hematuria, and major genitourinary tract disease., Methods: To determine the incidence, prevalence, and cause of microscopic hematuria, patients receiving long-term anticoagulation therapy and controls not receiving such therapy were monitored with monthly urinalyses in a 2-year prospective study. Patients who developed hematuria were further studied for genitourinary tract disease. The incidence of hematuria was analyzed with regard to relative levels of anticoagulation., Results: The incidence of hematuria in the anticoagulated and control groups was 0.05 and 0.08 per 100 patient-months, respectively. The prevalence of hematuria was 3.2% in the anticoagulated group and 4.8% in the control group. Genitourinary tract disease was identified in 81% of patients with more than one episode of microscopic hematuria, and the cause of hematuria did not vary between groups. There was no correlation between the level of anticoagulation and the incidence of hematuria., Conclusions: Anticoagulation at currently recommended levels does not predispose patients to hematuria. Identifiable genitourinary tract disease is present in the majority of anticoagulated patients with microscopic hematuria.

Two cases of Wegener's granulomatosis presenting with prostatic involvement are described and compiled with the five previously detailed cases. Each of these patients presented with obstructive symptoms, proteinuria, leukocyturia, and hematuria. The urinary sediment normalized with treatment of the underlying granulomatous vasculitis. Wegener's granulomatosis is a rare cause of prostatic obstructive symptoms, but should be considered whenever the relatively unusual entity of granulomatous prostatitis is diagnosed. One patient was initially treated exclusively with trimethoprim-sulfamethoxazole (TMP-SMX). He responded, but noted recurrence during the 15th month of treatment. We also report on this patient's antineutrophil cytoplasmic antibody (ANCA) titers, which correlated with clinical assessment and predicted recurrence 2 months before elevation of the Westergren sedimentation rate (WSR) and clinical diagnosis.

Byssinosis is an occupational respiratory disease contracted by cotton mill workers who inhale cotton mill dust. The acute byssinotic reaction is characterized by a drop in the 1-sec forced expiratory volume (FEV1.0) on Monday following a weekend's absence from work. This physiological reaction is the result of the contraction of bronchial smooth muscle, which causes narrowing of small airways. An isolated tissue bath technique was used to assay smooth muscle contractions induced by cotton dust extract (CDE) and cotton bract extract (CBE). CBE-induced contractions of rat stomach smooth muscle were blocked (82%) by 100 ng/ml methysergide (blocks 5-hydroxytryptamine (5HT) 100%); CDE was not significantly blocked by methysergide (13%). CDE-induced contractions were blocked (100%) by 25 micrograms/ml indomethacin and 100 micrograms/ml salicylic acid (blocks prostaglandin F2 alpha (PGF2 alpha) 100%). The portion of CBE contracting ability not blocked by methysergide was blocked totally by indomethacin. Blocking agents ineffective against CDE or CBE include atropine (acetylcholine blocker), pyrilamine maleate and diphenhydramine (histamine blockers), imidazole and 7-(1-imidazolyl)heptanoic acid (7IHA) (thromboxane blockers), and carboxypeptidase B2 (kinin blocker). The data suggest that cotton bract contains 5HT, which is responsible for a majority of the CBE-induced contraction and a minority of the CDE-induced contraction. The data also suggest that cotton dust and bract contain a substance which causes the release of PGF2 alpha which in turn causes the contraction of smooth muscle. This substance is responsible for a majority of the CDE-induced and a minority of the CBE-induced contractions. Radioimmunoassay (RIA) confirmed PGF2 alpha release from rat fundal smooth muscle when exposed to CDE and CBE. Increased synthesis and release of arachidonic acid metabolites might be a major mechanism in the bronchoconstriction observed in the acute byssinotic reaction.