Comparative study of the Martian suprathermal electron depletions based on Mars Global Surveyor, Mars Express and Mars Atmosphere and Volatile EvolutioN missions observations

Nightside suprathermal electron depletions have been observed at Mars by three spacecraft to date: Mars Global Surveyor, Mars Express, and the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. This spatial and temporal diversity of measurements allows us to propose here a comprehensive view of the Martian electron depletions through the first multispacecraft study of the phenomenon. We have analyzed data recorded by the three spacecraft from 1999 to 2015 in order to better understand the distribution of the electron depletions and their creation mechanisms. Three simple criteria adapted to each mission have been implemented to identify more than 134,500 electron depletions observed between 125 and 900 km altitude. The geographical distribution maps of the electron depletions detected by the three spacecraft confirm the strong link existing between electron depletions and crustal magnetic field at altitudes greater than ~170 km. At these altitudes, the distribution of electron depletions is strongly different in the two hemispheres, with a far greater chance to observe an electron depletion in the Southern Hemisphere, where the strongest crustal magnetic sources are located. However, the unique MAVEN observations reveal that below a transition region near 160–170 km altitude the distribution of electron depletions is the same in both hemispheres, with no particular dependence on crustal magnetic fields. This result supports the suggestion made by previous studies that these low-altitudes events are produced through electron absorption by atmospheric CO2

Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology

OBJECTIVE: To use next generation sequencing (NGS) technology to identify undiagnosed, monogenic diseases in a cohort of children who suffered from acute liver failure (ALF) without an identifiable etiology. STUDY DESIGN: We identified 148 under 10 years of age admitted to King's College Hospital, London, with ALF of indeterminate etiology between 2000 and 2018. A custom NGS panel of 64 candidate genes known to cause ALF and/or metabolic liver disease was constructed. Targeted sequencing was carried out on 41 children in whom DNA samples were available. Trio exome sequencing was performed on 4 children admitted during 2019. A comparison of the clinical characteristics of those identified with biallelic variants against those without biallelic variants was then made. RESULTS: Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively. The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). The 12 children who were identified with biallelic variants were younger at presentation and more likely to die in comparison with those who did not: median age at presentation of 3 months and 30 months and survival rate 75% and 97%, respectively. CONCLUSIONS: NGS was successful in identifying several specific etiologies of ALF. Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings. In the future, a rapid sequencing NGS workflow could help in reaching a timely diagnosis and facilitate clinical decision making in children with ALF

Properties of a large-scale flux rope and current sheet region on the dayside of Mars: MGS MAG/ER and MEX ASPERA-3 ELS observations

We present dual spacecraft observations by MGS MAG/ER and MEX ASPERA-3 ELS of a large-scale magnetic flux rope on the dayside of Mars that occurs in close proximity to the crustal magnetic fields and a dayside current sheet region. A current sheet (including the large-scale flux rope) was observed on repeated MGS orbits when the draped solar wind magnetic field present in the ionosphere had a +B component (in MSO). Minimum Variance Analysis (MVA) of the large-scale flux rope and two current sheet crossings that occur after show a common peak in magnetic field along the intermediate variance direction, indicating the normal component of a reconnecting current sheet. All repeated orbits demonstrated evidence of a plasma boundary by the decrease in electron differential flux above 100eV when moving into regions dominated by the crustal magnetic field, and coincided with the measured magnetic field strength being double the undisturbed crustal magnetic field. We argue this forms evidence of magnetic reconnection between crustal magnetic fields and draped solar wind magnetic field (from ionosphere or magnetosheath) at a "mini-magnetopause" type boundary on the dayside of Mars. Similar electron pitch angle distributions observed during the large-scale flux rope, current sheet crossings, and regions of radial crustal magnetic field, suggest these regions share a common magnetic field topology for the trapping of magnetosheath particles on open crustal magnetic fields on the dayside of Mars. As such, indicates a trapping quadrupole magnetic field exist either at the magnetic reconnection X-line region or where open crustal magnetic fields meet oppositely directed solar wind magnetic field. At a time when the draped solar wind magnetic field present in the ionosphere was weaker in strength, the current sheet crossing was observed over an extended region of 2000km. The extended current sheet demonstrated properties of a hot diamagnetic region and features of a mirror mode structure or magnetic hole, the first time such a structure has been found in the ionosphere of Mars. Observations suggests lower energy electrons could be accelerated by a local process of perpendicular heating/pitch angle diffusion and supports similar results at the Earth's polar cusp reported by Nykyri et al. (Nykyri et al. [2012]. J. Atmos. Sol-Terr. Phys. 87, 70). Such large scale and energetic structures are usually associated with regions beyond a planet's ionosphere, and the occurrence within the ionosphere of Mars may have an important impact on escape processes and the evolution of the martian atmosphere

The Impact of Shame, Self-Criticism and Social Rank on Eating Behaviours in Overweight and Obese Women Participating in a Weight Management Programme

Recent research has suggested that obesity is a stigmatised condition. Concerns with personal inferiority (social rank), shame and self-criticism may impact on weight management behaviours. The current study examined associations between social comparison (shame, self-criticism), negative affect and eating behaviours in women attending a community based weight management programme focused on behaviour change. 2,236 participants of the programme completed an online survey using measures of shame, self-criticism, social comparison, and weight-related affect, which were adapted to specifically address eating behaviour, weight and body shape perceptions. Correlation analyses showed that shame, self-criticism and social comparison were associated with negative affect. All of these variables were related to eating regulation and weight control (p < 0.001). Path analysis revealed that the association of shame, hated-self, and low self-reassurance on disinhibition and susceptibility to hunger was fully mediated by weight-related negative affect, even when controlling for the effect of depressive symptoms (p < 0.050 to p < 0.010). In addition, feelings of inadequacy and unfavourable social comparisons were associated with higher disinhibition and susceptibility to hunger, partially mediated through weight-related negative affect (p = 0.001). These variables were negatively associated with extent of weight loss during programme attendance prior to the survey, while self-reassurance and positive social comparisons were positively associated with the extent of weight loss prior to the survey (p < .050). Shame, self-criticism, and perceptions of inferiority may play a significant role in self-regulation of eating behaviour in overweight people trying to manage their weight

Low Density Lipoprotein Receptor-Related Protein 1 Dependent Endosomal Trapping and Recycling of Apolipoprotein E

BACKGROUND: Lipoprotein receptors from the low density lipoprotein (LDL) receptor family are multifunctional membrane proteins which can efficiently mediate endocytosis and thereby facilitate lipoprotein clearance from the plasma. The biggest member of this family, the LDL receptor-related protein 1 (LRP1), facilitates the hepatic uptake of triglyceride-rich lipoproteins (TRL) via interaction with apolipoprotein E (apoE). In contrast to the classical LDL degradation pathway, TRL disintegrate in peripheral endosomes, and core lipids and apoB are targeted along the endocytic pathway for lysosomal degradation. Notably, TRL-derived apoE remains within recycling endosomes and is then mobilized by high density lipoproteins (HDL) for re-secretion. The aim of this study is to investigate the involvement of LRP1 in the regulation of apoE recycling. PRINCIPAL FINDINGS: Immunofluorescence studies indicate the LRP1-dependent trapping of apoE in EEA1-positive endosomes in human hepatoma cells. This processing is distinct from other LRP1 ligands such as RAP which is efficiently targeted to lysosomal compartments. Upon stimulation of HDL-induced recycling, apoE is released from LRP1-positive endosomes but is targeted to another, distinct population of early endosomes that contain HDL, but not LRP1. For subsequent analysis of the recycling capacity, we expressed the full-length human LRP1 and used an RNA interference approach to manipulate the expression levels of LRP1. In support of LRP1 determining the intracellular fate of apoE, overexpression of LRP1 significantly stimulated HDL-induced apoE recycling. Vice versa LRP1 knockdown in HEK293 cells and primary hepatocytes strongly reduced the efficiency of HDL to stimulate apoE secretion. CONCLUSION: We conclude that LRP1 enables apoE to accumulate in an early endosomal recycling compartment that serves as a pool for the intracellular formation and subsequent re-secretion of apoE-enriched HDL particles

Initial validation of the mindful eating scale

Published Mindfulness, 2013, 5(6), pp. 719-729. The final publication is available at Springer via http://dx.doi.org/10.1007/s12671-013-0227-5Self-report scales for mindfulness are now widely used in applied settings, and have made a contribution to research, for instance in demonstrating mediation effects. To date there are no convincing data as to whether mindfulness skills generalise fully across life domains, and so some researchers have developed mindfulness scales for particular domains of behaviour. We present the development of a self-report scale to measure mindfulness with respect to eating behaviours

Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typically reveal either suppressed or drastically enhanced EAA symmetry depending mainly on the horizontal extent of the heat flux anomaly. Our results suggest that the length scale of the anomaly should be on the same order as the outer core radius to significantly affect flow and field symmetries. As an implication to Mars and in the range of our model, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heterogeneously magnetise the crust to the present-day level of north–south asymmetry on Mars. The resulting magnetic fields obtained using our model either are not asymmetric enough or, when they are asymmetric enough, show rapid polarity inversions, which are incompatible with thick unidirectional magnetisation

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402