One common approach for solving collisions between protoplanets in simulations of planet formation is to employ analytical scaling laws. The most widely used one was developed by Leinhardt & Stewart ...(2012, ApJ, 745, 79) from a catalog of ~180
N
-body simulations of rubble–pile collisions. In this work, we use a new catalogue of more than 20 000 SPH simulations to test the validity and the prediction capability of Leinhardt & Stewart (2012, ApJ, 745, 79) scaling laws. We find that these laws overestimate the fragmentation efficiency in the merging regime and they are not able to properly reproduce the collision outcomes in the super-catastrophic regime. In the merging regime, we also notice a significant dependence between the collision outcome, in terms of the largest remnant mass, and the relative mass of the colliding protoplanets. Here, we present a new set of scaling laws that are able to better predict the collision outcome in all regimes and it is also able to reproduce the observed dependence on the mass ratio. We compare our new scaling laws against a machine learning approach and obtain similar prediction efficiency.
Le progrès des connaissances sur la sclérose latérale amyotrophique a conduit au développement du premier et, à ce jour, seul traitement étiologique, le riluzole, dont l’efficacité a été prouvée dans ...deux essais cliniques contrôlés. Ces études ont montré que le riluzole augmente le taux de survie des patients de l’ordre de 25 p. 100 sur une période de 12 mois de traitement. Depuis sa commercialisation, son bénéfice clinique a également été confirmé dans plusieurs études épidémiologiques. Au départ, le riluzole a été proposé en raison de ses qualités anti-glutamates, mais les mécanismes d’action exacts responsables de ses effets dans la SLA demeurent encore inconnus. Par ailleurs, plusieurs molécules anti-glutamates ont été essayées sans succès dans cette maladie, ainsi que de nombreuses molécules anti-oxydantes, neurotrophiques, immunomodulatrices, et favorisant le métabolisme mitochondrial. Tous ces essais se sont révélés négatifs, et cela malgré des pré requis qui semblaient solides et basés sur une littérature riche. Malgré le faible taux d’augmentation des transaminases, un traitement par riluzole nécessite un contrôle strict des fonctions hépatiques. En cas de fatigue importante, d’altération de l’état général ou d’insuffisance respiratoire, sa posologie devrait être administrée et augmentée de façon progressive. Si l’on se base sur les qualités neuroprotectrices du riluzole, la présence d’une mort neuronale précoce dans la SLA, la difficulté à confirmer rapidement le diagnostic, et l’intérêt évident à traiter précocement, le traitement des formes suspectées de la maladie devient légitime. Les perspectives de traitement étiologique de la SLA dépendront de notre capacité à mieux en comprendre la physiopathologie ou les causes d’échecs dans le passé ainsi que du développement de nouveaux bio marqueurs. Mais elles dépendront aussi de notre capacité à réaliser des essais cliniques de longue durée et portant sur un nombre important de patients. De nouvelles méthodes, telle que la thérapie cellulaire, sont actuellement en développement et représentent un véritable espoir pour l’avenir.
The increasing knowledge about Amyotrophic Lateral sclerosis (ALS) led to the development of the first and only available treatment: riluzole. The efficacy of this drug has been demonstrated in two controlled clinical trials. The data showed that riluzole increases the rates of survival in patients suffering from ALS. This increase was about 25 percent over a period of 12 months of treatment. Since its marketing, the clinical efficacy of riluzole was confirmed in several epidemiological studies. Tested initially because of its anti-glutamates qualities, the exact mechanisms of action responsible for the efficacy of Riluzole in ALS remains unknown. Furthermore, despite a strong rational based on important literature, several other anti-glutamates drugs failed to demonstrate efficacy in ALS, nor did numerous anti-oxydant, neurotrophics, immunomodulators, and favoring mitochondrial metabolism drugs. Despite the low rate of patients showing an increase of liver enzymes, a strict control of liver functions is necessary with a treatment by riluzole. its dose should be increased gradually in case of important fatigue, a change of the general state, or respiratory incapacity. Because of the neuroprotectrives qualities of riluzole, early neuronal death in ALS, the difficulty to confirm early the diagnosis, and the evident interest to treat in the first stage, the treatment of the suspected forms of the disease becomes justifiable. The perspectives of treatment of ALS will depend on our capacity to understand better the physiopathology, the reasons of failures in the past, and to develop new biomarkers. They will depend also on our capacity to include in clinical trials and to follow up over a long time, an important number of patients. Different new methods, as the cellular therapy are in development, and represent a real hope for the future.
Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological ...outcomes of neonates with hypoxic-ischemic encephalopathy (HIE).
We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and melatonin/hypothermia group (N=15; received hypothermia and five daily enteral doses of melatonin 10 mg kg(-1)). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants (N=45) and at 5 days for the HIE groups (N=30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months.
Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin (P<0.001) and decline in NO (P<0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P<0.001).
Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.
Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC ...regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.
This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.
This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).
NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Retinopathy of prematurity (ROP) constitutes a significant morbidity in premature infants that can lead to blindness. Multiple retrospective studies have identified neonatal hyperglycemia as a risk ...for developing ROP. However, in the absence of any reported prospective study, it is not clear whether hyperglycemia is associated with ROP independent of the commonly associated comorbidities. The objective of this study was to investigate whether hyperglycemia in premature infants is independently associated with ROP.
Premature infants (<1500 g or⩽32 weeks gestational age) were enrolled in a prospective longitudinal cohort study. All demographic, clinical and laboratory data were collected. Bedside whole-blood glucose concentration was measured every 8 h daily for 7 days. For any glucose reading<50 or>150 mg dl(-1), serum sample was sent to the laboratory for confirmation. Hyperglycemia was defined as any blood glucose level⩾150 mg dl(-1). ROP patients were compared with non-ROP patients in a bivariate analysis. Variables significantly associated with ROP were studied in a logistic regression model.
A total of 65 patients were enrolled with gestational age 31.1±1.2 weeks and birth weight 1385±226 g. Thirty-one patients (48%) were identified with hyperglycemia. On eye examination, 19 cases (29.2%) had ROP (13 with stage 1, 4 with stage 2 and 2 with stage 3). There were more cases of ROP in the hyperglycemia group compared with the euglycemia group (45% vs 15%, P=0.007). Patients who developed ROP had significantly higher maximum and average glucose concentrations when compared with non-ROP patients. Multiple factors have been associated with ROP on bivariate analysis, including gestational age, exposure to oxygen, respiratory support and poor weight gain. However, in a logistic regression model including all significant variables, average blood glucose in the first week of life was the factor independently associated with ROP with an odds ratio of: 1.77 (95% confidence interval: 1.08 to 2.86), P=0.024.
In a cohort of premature infants, elevated average blood glucose concentrations in the first week of life is independently associated with the development of ROP.
•Determination of minimum chip thickness by means of cutting forces from dynamometer.•Determination of efficient sampling frequency in micomilling process.•Describe micromilling process dynamics on ...the periodicity of the cutting forces signal.•Characterization of the effect of cutting edge radius upon cutting forces during chip formation and.•Modelling of ploughing process by means of cutting force signal.
Issues related to ploughing affecting the performance of the micromilling process have recently been reported in literature. It is well known that there is a minimum chip thickness (hmin) below which ploughing is the main material removal mechanism and no shear occurs. This leads to a non-effective material removal, resulting in a poor surface quality. In order to solve this problem, the minimum chip thickness has been predicted by measuring the cutting forces. However, the determination of hmin by means of the cutting force signal, at the instant the chip is being formed, has not been approached. In this article, a method of determining hmin, based upon the signal variation of the cutting forces and the effect of tool radial runout during chip formation is proposed. Carbide micro-endmills without coating were used to cut an aluminium alloy (RSA 6061-T6) sample and the cutting forces were measured using a micro-dynamometer. The microtopography of a microchannel wall was assessed using an optical profiler in order to establish the approximate position where the chip starts to form (hmin). As the cut progresses, the force component normal to the feed (FfN) reverses when the undeformed chip thickness is equal to the cutting edge radius (re). Simultaneously, the thrust force increases rapidly, and continues to grow but at a lower rate as FfN increase. The main cutting force and the active force present significant differences to each other. The minimum chip thickness was estimated as 0.3re by means of the behavior of the active force. A small quantity of material left on the wall of the microchannel could be observed in align with the cutting movement together with a deterioration of the surface finish attributed to the increase of re. Results show that the size of the material left is 2 to 4 times greater than hmin. Conversely, the quality of the microchannel floor improves as re increase. This shows that there is a balance between hmin and re and the effect upon the finish of the channel wall and floor. That should be important for microchannel fabrication in terms of performance of micro-scale heat exchangers depending on fluid viscosity. The topographic analyses of the wall and the images of the chips show an agreement with estimated hmin under different cutting conditions and cutting edge radii. The proposed method in this paper not only permits the determination of the minimum chip thickness but also has the advantage of making it possible to estimate the cutting edge radius and to monitor the cutting edge wear.
MR imaging has a key role in predicting neurodevelopmental outcomes following neonatal hypoxic-ischemic encephalopathy (HIE). A novel MR imaging scoring system for hypoxic-ischemic brain injury was ...used in our patient population with the aim of assessing interobserver variability and developing subcategories for the severity of brain injury.
We evaluated brain MR images of 252 infants who underwent hypothermia for HIE between 2014 and 2019. First, 40 infants were selected randomly to test interobserver variability. Discrepancies were identified during the assessment of the first 20 MR images. The remaining 20 MR images were scored after adjusting the scoring system. Second, we determined cutoff values for the severity of injury that were based on the percentiles of the total scores in the full cohort.
The interobserver reliability showed excellent agreement for the total score both before (intraclass correlation coefficient = 0.96; 95% CI 0.89-0.99) and after the adjustment (intraclass correlation coefficient = 0.96; 95% CI, 0.89-0.98). The average of the differences and the agreement interval between the 2 readers decreased after the adjustment. Subcategories of brain injury were the following: We considered a total score of ≤4 (≤75%) as normal, 5-10 (76%-90%) as mild, 11-15 (91%-95%) as moderate, and >15 (>95%) as severe brain injury. The agreement on the classification of brain injury improved in the second epoch (weighted κ = 0.723 versus 0.887).
The adjusted scoring system may lead to a higher degree of interrater agreement. The presented cutoff values may be used to determine the severity of brain injury in future clinical studies including infants with mild hypoxia-ischemia.
Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions ...represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today.
This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.
We address the problem of the sequestration of Ar, Kr, and Xe by H super(+) sub(3) in the gas-phase conditions encountered during the cooling of protoplanetary disks when H super(+) sub(3) is ...competing with other species present in the same environment. Using high-level ab initio simulations, we try to quantify other sequestration possibilities involving He, H super(+) sub(5), H sub(2)O, and H sub(3)O super(+) present in the protosolar nebula. Apart from the fact that H super(+) sub(3) complexes formed with heavy noble gases are found to be by far much more stable than those formed with He or H sub(2)O, we show that H sub(2)D super(+) and H sub(3)O super(+), both products of the reactions of H super(+) sub(3) with HD and H sub(2)O, can also be efficient trapping agents for Ar, Kr, and Xe. Meanwhile, the abundance profile of H super(+) sub(3) in the outer part of the nebula is revisited with the use of an evolutionary accretion disk model that allows us to investigate the possibility that heavy noble gases can be sequestered by H super(+) sub(3) at earlier epochs than those corresponding to their trapping in planetesimals. We find that H super(+) sub(3) might be abundant enough in the outer protosolar nebula to trap Xe and Kr prior their condensation epochs, implying that their abundances should be solar in Saturn's current atmosphere and below the observational limit in Titan. The same scenario predicts that comets formed at high heliocentric distances should also be depleted in Kr and Xe. In situ measurements, such as those planed with the Rosetta mission on 67P/Churyumov-Gerasimenko, will be critical to check the validity of our hypotheses.
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