Author Correction: Rock fluidization during peak-ring formation of large impact structures.

In this Article, the middle initial of author Kosei E. Yamaguchi (of the IODP-ICDP Expedition 364 Science Party) was missing and his affiliation is to Toho University (not Tohu University). These errors have been corrected online.

Rock fluidization during peak-ring formation of large impact structures.

Large meteorite impact structures on the terrestrial bodies of the Solar System contain pronounced topographic rings, which emerged from uplifted target (crustal) rocks within minutes of impact. To flow rapidly over large distances, these target rocks must have weakened drastically, but they subsequently regained sufficient strength to build and sustain topographic rings. The mechanisms of rock deformation that accomplish such extreme change in mechanical behaviour during cratering are largely unknown and have been debated for decades. Recent drilling of the approximately 200-km-diameter Chicxulub impact structure in Mexico has produced a record of brittle and viscous deformation within its peak-ring rocks. Here we show how catastrophic rock weakening upon impact is followed by an increase in rock strength that culminated in the formation of the peak ring during cratering. The observations point to quasi-continuous rock flow and hence acoustic fluidization as the dominant physical process controlling initial cratering, followed by increasingly localized faulting.

Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men.

BACKGROUND: Exogenous glucagon-like peptide-1 (GLP-1) inhibits eating in healthy, overweight, and diabetic subjects. OBJECTIVE: The GLP-1 receptor antagonist exendin(9-39)NH2 (ex9-39) was used to further explore the role of GLP-1 as an endogenous satiation signal. DESIGN: Two double-blind, 4-way crossover studies were performed, each of which included 10 healthy men. In study A, subjects received an intravenous infusion of ex9-39 or saline plus an oral glucose preload and an intraduodenal infusion of saline or glucose for 60 min. In study B, intravenous infusions were identical, but an oral mixed-liquid meal preload and a 60-min intraduodenal infusion of saline or oleic acid were administered. Thirty minutes after oral preloads, subjects ate and drank ad libitum, and amounts ingested and the time to meal completion were quantified. In addition, appetite and plasma GLP-1, peptide YY (PYY), insulin, glucagon, and blood glucose concentrations were measured. RESULTS: In both studies, GLP-1, PYY, and glucagon were substantially higher with intravenous ex9-39 than with intravenous saline (P ≤ 0.001). Insulin was lower with intravenous ex9-39 during intraduodenal glucose (P ≤ 0.05). The decrease in prospective food consumption and desire to eat during ad libitum eating after glucose ingestion was slightly attenuated (P ≤ 0.05 and P ≤ 0.01, respectively) with ex9-39. However, with intravenous ex9-39, food and fluid intakes and eating duration were not changed in either study. CONCLUSIONS: GLP-1 receptor antagonism slightly modulates appetite during ad libitum eating, but food and fluid intakes and meal duration remain unchanged, suggesting that endogenous GLP-1 is a weak satiation signal. However, concomitant substantial increases in plasma PYY and glucagon may counteract a desatiating effect of ex9-39. The effect of ex9-39 on PYY secretion supports an autoinhibitory feedback mechanism that controls L cell secretion; the effect on insulin and glucagon confirms the role of GLP-1 in glycemic control through its action on pancreatic α and ß cells.

Gastric and intestinal satiation in obese and normal weight healthy people.

OBJECTIVE: The gastrointestinal tract plays a key role in feelings of satiation. It is known that there is a reciprocal interaction between the stomach and intestine, but it is not known which factors are of gastric origin and which are intestinal. This three-step study therefore sought to provide illumination on satiation parameters with respect to body mass. METHOD: In the first part, the time needed to reach maximal satiation and total caloric intake was calculated after participants (20 normal weight, 20 obese) imbibed a standardized nutrient drink. In the second part gastric emptying of solids and liquids was evaluated using the (13)C-breath test (participants: 16 normal weight, 9 obese for gastric emptying of solids; 15 normal weight, 14 obese for gastric emptying of liquids). And in the third part, fasting and post-prandial plasma glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY) and ghrelin levels were measured after a standardized nutrient drink (participants: 20 normal weight, 20 obese). RESULTS: Our results show that, when compared to those of normal weight, obese participants reached maximal satiation sooner (P=0.006), their total intake of calories was higher (P=0.013), and their gastric emptying rates were delayed (P<0.001). Furthermore, their post-prandial increase in plasma GLP-1 and PYY was reduced, (P<0.001 for both), as was their ghrelin suppression (P=0.001). DISCUSSION: We conclude that, in obese subjects gastric emptying can be impaired with delayed interaction of nutrients with the intestine resulting in decreased GLP-1 and PYY secretion. This could imply that obese participants would require more calories before their maximal satiation is reached and they stop eating.

Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count.

AIM: To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/µL ascites. METHODS: In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentian-violet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue(®) Reader (Bühlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/µL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values. RESULTS: The PMN count was > 250/µL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/µL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman's rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 µg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 µg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/µL, by both ELISA [median (IQR) 2.48 µg/mL (1.61-3.65) vs 0.10 µg/mL (0.10-0.36), P < 0.001] and POC [2.78 µg/mL (2.05-5.37) vs 0.38 µg/mL (0.38-0.41), P < 0.001]. The area under the receiver operating characteristics curve for identifying an elevated PMN count was 0.977 (95%CI: 0.933 to 0.995) for ELISA and 0.982 (95%CI: 0.942 to 0.997) for POC (P = 0.246 vs ELISA). Using the optimal cut-off value for ELISA (0.63 µg/mL), ascitic calprotectin had 94.8% sensitivity, 89.2% specificity, positive and negative likelihood ratios of 8.76 and 0.06 respectively, positive and negative predictive values of 60.0% and 99.0% respectively, and 90.0% overall accuracy. Using the optimal cut-off value for POC (0.51 µg/mL), the respective values were 100.0%, 84.7%, 6.53, 0.00, 52.8%, 100% and 87.7%. Correlation between ELISA and POC was excellent (r = 0.873, P < 0.001). The mean ± SD of the difference was -0.11 ± 0.48 µg/mL with limits of agreement of + 0.8 µg/mL (95%CI: 0.69 to 0.98) and -1.1 µg/mL (95%CI: -1.19 to -0.91). CONCLUSION: Ascitic calprotectin reliably predicts PMN count > 250/µL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.

The clinical profile and outcomes associated with coronary collaterals in patients with coronary artery disease.

BACKGROUND: The clinical correlates of coronary collaterals and the effects of coronary collaterals on prognosis are incompletely understood. METHODS: We performed a study of 55,751 patients undergoing coronary angiography to evaluate the correlates of angiographically apparent coronary collaterals, and to evaluate their association with survival. RESULTS: The characteristic most strongly associated with the presence of collaterals was a coronary occlusion (odds ratio [OR], 28.9; 95% confidence interval [CI], 27.1-30.6). Collaterals were associated with improved adjusted survival overall (hazard ratio [HR] 0.89; 95% CI, 0.85-0.95), and in both acute coronary syndrome (ACS) (HR 0.90; 95% CI, 0.84-0.96) and non-ACS (HR 0.84; 95% CI, 0.77-0.92) patients. Collaterals were associated with improved survival in those receiving angioplasty (HR 0.78; 95% CI, 0.71-0.85) and those with low risk anatomy treated medically (HR 0.84; 95% CI, 0.72-0.98), but not for those treated with coronary bypass graft surgery or those with high-risk anatomy treated without revascularization. CONCLUSIONS: The major correlate of coronary collaterals is the presence/extent of obstructive coronary artery disease. Collaterals are associated with better survival overall and in both ACS and non-ACS presentations, but not for those treated with coronary artery bypass graft (CABG) or those with high-risk anatomy who are not revascularized.

Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure.

We studied the acute effect of high-intensity interval exercise on biventricular function using cardiac magnetic resonance imaging in nine patients [age: 49 ± 16 yr; left ventricular (LV) ejection fraction (EF): 35.8 ± 7.2%] with nonischemic mild heart failure (HF). We hypothesized that a significant impairment in the immediate postexercise end-systolic volume (ESV) and end-diastolic volume (EDV) would contribute to a reduction in EF. We found that immediately following acute high-intensity interval exercise, LV ESV decreased by 6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty minutes following exercise (+30 min), there was an absolute increase in LV EF of 2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced immediately following exercise. Similar responses were observed for right ventricular volumes. Early filling velocity, filling rate, and diastolic annular velocity remained unchanged, while LV untwisting rate increased 24% immediately following exercise (P < 0.05) and remained 18% above baseline at +30 min (P < 0.05). The major novel findings of this investigation are 1) that acute high-intensity interval exercise decreases the immediate postexercise LV ESV and increases LV EF at +30 min in patients with mild HF, and this is associated with a reduction in LV afterload and maintenance of contractility, and 2) that despite a reduction in left atrial volume and LV EDV immediately postexercise, diastolic function is preserved and may be modulated by enhanced LV peak untwisting rate. Acute high-intensity interval exercise does not impair postexercise biventricular function in patients with nonischemic mild HF.

Ipsilateral submandibular lymphadenectomy does not prolong orthotopic corneal graft survival in mice.

PURPOSE: To explore the impact of selective lymphadenectomy on the outflow from the outer eye and corneal graft survival in mice. METHODS: BALB/c mice underwent submandibular lymphadenectomy either on the left side 7 or 21 days before the experiments or bilaterally 7 days in advance. First, (99m)Tc colloidal albumin (Nanocoll) was given as a subcutaneous lower-lid, upper-lid or subconjunctival injection, and count rates were determined 24 h later in the eyes, submandibular lymph nodes, spleen, liver and blood. Second, corneal graft survival was assessed in lymphadenectomised and control mice, and IFN-gamma secretion was determined in draining lymph nodes at the time of transplant rejection. RESULTS: Following subconjunctival Nanocoll injection, count rates/min/mg tissue were significantly higher in the ipsilateral submandibular lymph node than in the other tissues or blood (<0.01). Ipsilateral lymphadenectomy prior to injection resulted in considerably increased count rates in contralateral nodes ( P<0.01), which were higher after injections into upper than into lower lids ( P=0.004). Bilateral submandibular lymphadenectomy led to enhanced count rates in the eyes, blood, spleen and liver (all P<0.01). Removal of the ipsilateral lymph node prior to corneal transplantation did not prolong allograft survival ( P>0.05) and considerably increased IFN-gamma secretion in contralateral nodes after prior removal of the ipsilateral ones paralleled transplant rejection. CONCLUSIONS: In mice, removed submandibular lymph nodes are functionally completely replaced by the contralateral nodes. These studies demonstrate for the first time lymphatic drainage crossing the midline of the body. Consequently, unilateral lymphadenectomy does not improve corneal graft survival.

Minimizing side effects of ballistic gene transfer into the murine corneal epithelium.

BACKGROUND: The beneficial effect of modulating an allospecific immune response by ballistic IL-4 and CTLA4 gene transfer to deliver minimalistic immunologically defined gene expression (MIDGE) vectors into the corneal epithelium was demonstrated in corneal transplantation. However, side effects reduced graft survival in control animals after ballistic transfer without DNA. METHODS: An adapter was constructed for the gene gun apparatus to enlarge and keep constant the distance between the gun and the cornea. Mice were treated by ballistic transfer of luciferase- or IL-10 -encoding MIDGE vectors using gold particles different in quantity, size and size uniformity. Levels of protein expression were determined. Treated corneas were observed under the scanning electron microscope and immunohistologically. Three groups of Balb/c (H-2d) mice received a C3H (H-2 k) corneal graft and two of them had gold particles delivered into the corneal epithelium by gene gun. RESULTS: Using the gene gun and the distance piece, scanning electron microscopy did not reveal morphological differences of the corneal surface compared with untreated corneas on day 2 and 5. Sagittal histological sections of the central cornea did not show an invasion of macrophages 24 h after treatment. The expression of luciferase and IL-10 was not reduced when a smaller amount of gold (0.1 mg instead of 0.5 mg) was employed. Ballistic gold treatment did not reduce graft survival. CONCLUSION: Ballistic gene transfer into the corneal epithelium allows high cytokine expression in the cornea without measurable side effects if an apparatus is used that is adapted for this specific purpose.