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In this work we study the variation of the MOID between encounters so that we can determine the keyholes that exist in the B-plane. We compare the different methods to propagate the orbits of asteroids between planetary close encounters.

Deep neural networks (NNs) are usually trained with unconstrained optimisation algorithms. With a reasoning similar to the constrained Kalman filter, incorporating known information in the form of equality constraints at certain checkpoints can potentially improve prediction accuracy. For continuous-time dynamical systems, the state constraints should be enforced in an ordinary differential equation (ODE) model which embeds NNs to represent a learned part of dynamics or a control policy. To this end, incremental correction methods are developed for post-processing of the dynamical systems modelled with NNs for which the parameters are determined by previous optimisation process. The proposed approach is to find a small amount of local correction needed to satisfy given state constraints with the updated solution. Algorithms for updating the neural network parameters and the control function are considered.

Several crucial developments in orbital mechanics are obtained through the method of averaging, which is equivalent to integrating only the dominant harmonics of the Fourier series of the dynamics. Frequency analysis of the trajectory expressed in orbital elements facilitates an in-depth understanding of Earth satellite dynamics, and facilitates the interpretation of numerical results from special perturbations within the theoretical framework of celestial mechanics. In this work, we examine recent Two-Line Element series for LAGEOS-1 in the frequency domain, highlighting the presence of short-periodic terms that are likely introduced in the generation of TLEs from observations. We also propose employing well-established methods from signal processing, such as spectrograms, to examine the evolution of dissipative systems such as satellites in LEO.

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P

This is the peer reviewed version of the following article: [Ruskey, J.A., Zhou, S., Santiago, R., Franche, L.-A., Alam, A., Roncière, L., Spiegelman, D., Fon, E.A., Trempe, J.-F., Kalia, L.V., et al. (2018). TheGBAp.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies. Clinical Genetics 94, 339–345.], which has been published in final form at https://doi.org/10.1111/cge.13405. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Close encounters with major Solar System bodies may bring about a strong amplification of numerical error during inter-planetary orbit propagation. In this work, we reduce global numerical error by integrating regularized equations of motion instead of the classical Newtonian equations in Cartesian coordinates. The integration performance of several sets ofregularized equations is assessed from large-scale numeri-cal propagations of close encounters in the Sun-Earth planar CR3BP. An essential device consists in switching between primary bodies during the propagation, which effectively decomposes a strongly-perturbed heliocentric problem into two weakly-perturbed ones; this propagation approach has been dubbed Online Trajectory Matching (OTM). Through this simple expedient, regularized equations describing the evolution of non-classical orbital elements achieve excellent performances compared to Newtonian equations, even when employing sophisticated adaptive numerical schemes.Further improvements might be expected by carefully selecting the location of the switch of primary bodies during the propagation.

OBJECTIVE To assess whether apparently healthy subjects with a family history of systemic hypertension have a higher risk of presenting the insulin resistance syndrome. SUBJECTS Three hundred and eighty-six subjects aged 20-65 years. SETTING A middle socio-economic class urban community from Mexico City. METHOD All subjects and, when necessary, their first-degree relatives, answered a questionnaire and underwent a physical examination with measurement of height, weight and blood pressure. Serum insulin, glucose, cholesterol and triglycerides were measured during fasting and 2 h after an oral load of 75 g glucose. RESULTS A family history of systemic hypertension was present for 167 (43%) of the subjects, of whom 123 (31%) were obese. Subjects with a family history of hypertension had higher systolic blood pressures than did those without such a history (120 +/- 15 versus 115 +/- 10 mmHg). In the logistic regression model, the body mass index and age showed statistically significant effects on the fasting glucose:insulin ratio and on serum insulin levels after an oral load of glucose. When men and women were analysed separately, only in men were higher systolic and mean blood pressures and lower glucose:insulin ratios observed. In the logistic regression analysis the body mass index was a significant predictor of the glucose:insulin ratio and serum insulin levels after an oral load of glucose, especially in men. CONCLUSION Apparently healthy male offspring of hypertensive parents have higher blood pressure levels and lower insulin sensitivities than do offspring of normotensive parents. Insulin resistance was related to obesity, but not to a family history of hypertension, as had previously been reported by other research groups.

The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response. From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest (ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria) and pathological response (assessed using Mandard's classification). Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evaluated the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values obtained with the two different methods of ROI placement were 1.11 and 1.02 × 10(-3) mm(2) /seconds. Mean post-treatment ADC values were 1.40 and 1.35 × 10(-3) mm(2) /seconds, respectively. A significant inverse correlation between mean ADC increase and Mandard's classifications was observed for both the methods of ADC measurements. Diagnostic performance analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method (accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides superior evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from nonresponder patients.

Peritoneal mesothelioma is a rare disease, especially when it arises in a cystic form with tardive and often nonspecific symptoms. While diffuse neoplasms have an unfavorable prognosis, cystic forms are usually benign. An accurate diagnosis can only be made only with electron microscopy and immunohistochemical studies. A 92-year-old woman with an ultrastructurally ascertained cystic peritoneal mesothelioma was admitted to the hospital's emergency ward, and was considered to be unusual because of the size of the mass and the patient's age. A review of the literature is made, and the clinical and diagnostic aspects of this disease are also discussed.

The authors report a case of isolated mesenteric fibromatosis un associated with familial adenomatous polyposis or Gardner's syndrome or prior abdominal surgery. These neoplasms are usually asymptomatic until when the compression of the small or large bowel or the ureter causes symptoms; although they are benign lesions without metastases, local recurrences are very frequent. Surgical removal is the primary treatment; until now no satisfactory results have been obtained with other therapeutic modalities.

Two cases in which a severe form of intestinal angina was cured by revascularization of an isolated hepatic artery were studied. The collateral pathways to the hepatic artery may serve, in a retrograde fashion, to assure an acceptable blood supply to the splanchnic organs, even when the disease of the 3 main vessels is so extensive that the commonly used techniques of revascularization cannot be applied. (J Vasc Surg 1998;28:1115-9.)

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Background: Magnetic resonance cholangiopancreatography (MRCP) is the gold standard for diagnosis of patients with primary sclerosing cholangitis (PSC). The semi-quantitative MRCP-derived Anali scores proposed for risk stratification, have poor-to-moderate inter-reader agreement. Aims: To evaluate the prognostic performance of quantitative MRCP metrics in PSC. Methods: This is a retrospective study of PSC patients undergoing MRCP. Images were processed using MRCP+ software (Perspectum Ltd, Oxford) that provides quantitative biliary features, semi-automatically extracted by artificial intelligence-driven analysis of MRCP-3D images. The prognostic value of biliary features has been assessed for all hepato-biliary complications. Results: 87 PSC patients have been included in the analysis. Median follow-up from MRCP to event/censoring of 30.9 months (Q1-Q3=13.6–46.6). An adverse outcome occurred in 27 (31.0%) patients. The number of biliary strictures (HR=1.05 per unit, 95%CI 1.02–1.08, p < 0.0001), spleen length (HR=1.16 per cm, 95%CI 1.01–1.34, p = 0.039), adjusted for height, age at MRCP, and time from diagnosis to MRCP predicted higher risk of hepatobiliary complications. These were incorporated into a the quantitative MRCP-derived PSC (qMRCP-PSC) score (C-statistic=0.80). After 3-fold cross-validation, qMRCP-PSC outperformed the Anali score in our cohort (C-statistic of 0.78 vs 0.64) and enabled the discrimination of survival of PSC patients (log-rank p < 0.0001). Conclusions: The qMRCP-PSC score identified patients at higher risk of hepatobiliary complications and outperformed the available radiological scores. It represents a novel quantitative biomarker for disease monitoring and a potential surrogate endpoint for clinical trials.

Background and Aims: Non-invasive evaluation of liver fibrosis in primary biliary cholangitis (PBC) with Liver Stiffness Measurements (LSM) by Transient Elastography (TE) is routinely undertaken at diagnosis for disease staging and risk stratification. However, evidence on correlation between LSM and liver fibrosis is based on cross-sectional studies in PBC-treated patients. Moreover, the impact of potential confounders, e.g. cholestasis and steatosis, is unclear. Aim of our study was to investigate the accuracy of LSM to predict moderate to severe fibrosis in newly diagnosed PBC patients naïve to therapy. Method: We collected data from 182 adult patients who underwent liver biopsy (LB) for PBC at diagnosis in five Italian liver centers from Jan 2006 through Aug 2019. TE examinations within 3 months from LB were included. LB were scored centrally by two expert pathologists, blinded to clinical data and disease stage, according to Ludwig staging system. In all patients Fibrosis-4 (FIB-4) and aspartate aminotransferase [AST]/platelet ratio (APRI) score have been calculated. Diagnostic accuracy of LSM, FIB-4 and APRI score was estimated using the area under the receiver operating characteristic curves (AUROCs) for fibrosis. The effects of liver biochemistry and histological parameters were appraised using multivariable logistic model. Results: 123 PBC patients had adequate LB (≥9 portal tracts) and valid LSM values. According to histological assessment, Ludwig stage distribution was as follows: stage I = 38 (30.9%), stage II = 46(37.4%), stage III = 27 (21.9%), stage IV = 12 (9.8%). TE identified patients with Ludwig stage III/IV with an AUROC of 0.83 (95% confidence interval [CI] (0.74, 0.90)) (Fig.1). The optimal threshold was identified at 6.75kPa (CI (6.55, 7.50)), with 85% of sensitivity, 75% of specificity, 78% of accuracy and 6 false negative. TE was superior to APRI and FIB-4 having AUROC of 0.638 (CI = (0.535, 0.740)) and 0.641 (CI = (0.516, 0.766)), respectively. At multivariable analysis only LSM was associated with liver fibrosis and no significant effect of biochemical measures and steatosis was found. Conclusion: LSM is accurate to predict moderate to severe liver fibrosis at diagnosis in PBC naïve patients using a threshold of 6.75kPa with an AUROC of 0.83. TE outperformed FIB-4 and APRI score and is not confounded by liver biochemistry and steatosis. These data can inform strategies for patient surveillance and trial design in PBC.

Primary biliary cholangitis and primary sclerosing cholangitis are rare diseases affecting the bile ducts and the liver. The limited knowledge of their pathogenesis leads to limited therapeutic options. Nevertheless, the landscape of novel therapies for these cholangiopathies is now rapidly changing, providing new treatment opportunities for patients and clinicians involved in their care. The aim of this review is to summarize the evidence of novel molecules under investigation for primary biliary cholangitis and primary sclerosing cholangitis and to discuss how they can potentially change current treatment paradigms.