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Background: Sedentary behavior, such as excessive sitting, increases risk of cardiovascular disease and premature mortality in the general population, but this has not been assessed in type 1 diabetes. Occupational sitting is increasingly ubiquitous and often constitutes the largest portion of daily sitting time. Our aim was to identify clinical factors associated with excessive occupational sitting in type 1 diabetes and, in a prospective setting, to explore its association with cardiovascular events and all-cause mortality, independent of leisure-time physical activity. Methods: An observational follow-up study of 1,704 individuals (mean age 38.9 ± 10.1 years) from the Finnish Diabetic Nephropathy Study. Excessive occupational sitting, defined as ≥ 6 h of daily workplace sitting, was assessed using a validated self-report questionnaire. Data on cardiovascular events and mortality were retrieved from national registries. Multivariable logistic regression identified independently associated factors, while Kaplan-Meier curves and Cox proportional hazard models were used for prospective analyses. Results: Factors independently and positively associated with excessive occupational sitting included a high occupational category [OR 6.53, 95% CI (4.09‒10.40)] and older age [1.02 (1.00‒1.03)], whereas negatively associated factors included current smoking [0.68 (0.50‒0.92)], moderate albuminuria [0.55 (0.38‒0.80)], and high leisure-time physical activity [0.52 (0.36‒0.74)]. During a median follow-up of 12.5 (6.5–16.4) years, 163 individuals (9.6%) suffered cardiovascular events, and during a median follow-up of 13.7 (9.4–16.6) years, 108 (6.3%) deaths occurred. Excessive occupational sitting increased cardiovascular event risk (hazard ratio [HR] 1.55 [95% CI 1.10‒2.18]) after adjustment for confounders and other covariates. Furthermore, in a stratified multivariable analysis among current smokers, excessive occupational sitting increased the risk of all-cause mortality (2.06 [1.02‒4.20]). Conclusions: Excessive occupational sitting is associated with a higher risk of cardiovascular events and all-cause mortality in individuals with type 1 diabetes. This association persists regardless of leisure-time physical activity, after adjusting for independently associated variables identified in our cross-sectional analyses. These findings underscore the need to update physical activity guidelines to better address sedentary behavior and improve outcomes for individuals with type 1 diabetes. Targeting occupational sitting should be considered a key focus for interventions aimed at reducing overall sedentary time. [ABSTRACT FROM AUTHOR]

Background: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. Methods: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. Results: During median 18.0 (14.1–19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no–very mild (ETDRS 10–20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02–3.15) in non-proliferative (ETDRS 35–53), and 1.69 (1.02–2.82) in proliferative (ETDRS 61–85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91–3.10) in non-proliferative and 1.35 (0.77–2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66–12.28) in non-proliferative and 4.31 (1.16–16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). Conclusions: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses. We therefore aimed to systematically investigate the prevalence of rare genetic variants causing inborn errors of immunity (IEI) and functionally interrogate the type I IFN pathway in young adults that suffered from critical COVID-19 yet lacked comorbidities. We selected and clinically characterized a cohort of 38 previously healthy individuals under 50 years of age who were treated in intensive care units due to critical COVID-19. Blood samples were collected after convalescence. Two patients had IFN-α autoantibodies. Genome sequencing revealed very rare variants in the type I IFN pathway in 31.6% of the patients, which was similar to controls. Analyses of cryopreserved leukocytes did not indicate any defect in plasmacytoid dendritic cell sensing of TLR7 and TLR9 agonists in patients carrying variants in these pathways. However, lymphocyte STAT phosphorylation and protein upregulation upon IFN-α stimulation revealed three possible cases of impaired type I IFN signaling in carriers of rare variants. Together, our results suggest a strategy of functional screening followed by genome analyses and biochemical validation to uncover undiagnosed causes of critical COVID-19. [ABSTRACT FROM AUTHOR]

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby‐Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs‐Buder et al., Acta Anaesthesiol Scand 2007, 51, 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three‐dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high‐quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus‐based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic neuropathy and diabetic eye disease are well known complications of type 1 diabetes. We hypothesized that chronic hyperglycemia also damages the optic tract, which can be measured using routine magnetic resonance imaging. Our aim was to compare morphological differences in the optic tract between individuals with type 1 diabetes and healthy control subjects. Associations between optic tract atrophy and metabolic measures, cerebrovascular and microvascular diabetic complications were further studied among individuals with type 1 diabetes. Methods: We included 188 subjects with type 1 diabetes and 30 healthy controls, all recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent a clinical examination, biochemical work-up, and brain magnetic resonance imaging (MRI). Two different raters manually measured the optic tract. Results: The coronal area of the optic chiasm was smaller among those with type 1 diabetes compared to non-diabetic controls (median area 24.7 [21.0-28.5] vs 30.0 [26.7-33.3] mm2, p<0.001). In participants with type 1 diabetes, a smaller chiasmatic area was associated with duration of diabetes, glycated hemoglobin, and body mass index. Diabetic eye disease, kidney disease, neuropathy and the presence of cerebral microbleeds (CMBs) in brain MRI were associated with smaller chiasmatic size (p<0.05 for all). Conclusion: Individuals with type 1 diabetes had smaller optic chiasms than healthy controls, suggesting that diabetic neurodegenerative changes extend to the optic nerve tract. This hypothesis was further supported by the association of smaller chiasm with chronic hyperglycemia, duration of diabetes, diabetic microvascular complications, as well as and CMBs in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD. Methods: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). Results: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74–83], 75 [70–80], and 75 [72–81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46–2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. Conclusions: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype. [ABSTRACT FROM AUTHOR]

Mars Express and Mars Atmosphere and Volatile Evolution (MAVEN) observations have demonstrated the influence of Mars's spatially variable crustal magnetic fields upon the configuration of the plasma in the ionosphere. This influence furthermore leads to variations in ionospheric escape, conceivably in part through the modification of the plasma density and electron temperature in the upper ionosphere. In this study, we examine MAVEN Langmuir Probe and Waves data, finding a clear correspondence between the structure of the crustal fields and both the measured electron temperatures and densities, by first constructing an "average" profile from which departures can be quantified. Electron temperatures are shown to be lower in regions of strong crustal fields over a wide altitude range. We extend previous analyses to cover the nightside ionosphere, finding the same effects present to a lesser degree, in contrast to previous studies where the opposite relationship was found between densities and crustal fields. We further determine the altitude range over which this coupling between both plasma density (and temperature) and crustal fields is effective and use measurements made by MAVEN in the solar wind to explore the dependence of this crustal field control on the coupling to the solar wind and the interplanetary magnetic field (IMF). Based on this, there is some suggestion that variations in the solar wind dynamic pressure are associated with modulation of the effects of the crustal fields on plasma density, whereas the strength of the IMF modulates the crustal fields effects on both electron densities and temperatures. Plain Language Summary: Mars's atmosphere is exposed to ultra‐violet light from the Sun, forming a layer of plasma at high altitudes around the planet. This plasma layer, termed the ionosphere, is strongly affected in terms of its density and temperature, both by external factors like the solar wind and the interplanetary magnetic field (IMF), and internal factors, like Mars's crustal magnetic field. Here, we study how effective the crustal magnetic fields are at shaping the ionosphere in both density and temperature, by first determining the average structure of the ionosphere, and then examining departures from this average. We find that plasma densities are elevated and temperatures reduced in regions where the crustal field is stronger. We also find the same effect on the nightside. This result is in apparent opposition to previous related studies, now based on a much larger data set, which we suggest may be the result of poor seasonal sampling in earlier studies. We further investigate how this crustal field control varies with the solar wind and IMF, and see evidence for weak modulation according to both the dynamic pressure exerted by the solar wind, and the strength of the IMF. Key Points: We present a statistical analysis of Mars Atmosphere and Volatile Evolution Langmuir Probe and Wave densities and temperatures at MarsDensities are elevated and temperatures reduced in strong crustal field regions, on both the dayside and nightsideVariations in the driving solar wind conditions are able to affect these correlations to a modest degree [ABSTRACT FROM AUTHOR]

The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future. [ABSTRACT FROM AUTHOR]

The exon copy number variant in the haptoglobin gene is associated with cardiovascular and kidney disease. For stroke, previous research is inconclusive. We aimed to study the relationship between the haptoglobin Hp1/2 genotype and stroke in individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study. We included two partially overlapping cohorts: one with haptoglobin genotypes determined using genotyping for 179 individuals with stroke and 517 matched control subjects, and the other using haptoglobin genotype imputation for a larger cohort of 500 individuals with stroke and 3,806 individuals without stroke. We observed no difference in the Hp1-1, Hp2-1, and Hp2-2 genotype frequencies between individuals with or without stroke, neither in the genotyping nor the imputation cohorts. Haptoglobin genotypes were also not associated with the ischemic or hemorrhagic stroke subtypes. In our imputed haptoglobin cohort, 61% of individuals with stroke died during follow-up. However, the risk of death was not related to the haptoglobin genotype. Diabetic kidney disease and cardiovascular events were common in the cohort, but the haptoglobin genotypes were not associated with stroke when stratified by these complications. To conclude, the Hp1/2 genotypes did not affect the risk of stroke or survival after stroke in our cohort with type 1 diabetes. [ABSTRACT FROM AUTHOR]

We investigate the role of secondary electron and ion emission from impact of gas molecules on the Cassini Langmuir probe (RPWS-LP or LP) measurements in the ionosphere of Saturn. We add a model of the emission currents, based on laboratory measurements and data from comet 1P/Halley, to the equations used to derive plasma parameters from LP bias voltage sweeps. Reanalysing several hundred sweeps from the Cassini Grand Finale orbits, we find reasonable explanations for three open conundrums from previous LP studies of the Saturn ionosphere. We find an explanation for the observed positive charging of the Cassini spacecraft, the possibly overestimated ionospheric electron temperatures, and the excess ion current reported. For the sweeps analysed in detail, we do not find (indirect or direct) evidence of dust having a significant charge-carrying role in Saturn's ionosphere. We also produce an estimate of H2O number density from the last six revolutions of Cassini through Saturn's ionosphere in greater detail than reported by the Ion and Neutral Mass Spectrometer. Our analysis reveals an ionosphere that is highly structured in latitude across all six final revolutions, with mixing ratios varying with two orders of magnitude in latitude and one order of magnitude between revolutions and altitude. The result is generally consistent with an empirical photochemistry model balancing the production of H+ ions with the H+ loss through charge transfer with e.g. H2O, CH4, and CO2, for which water vapour appears as the likeliest dominant source of the signal in terms of yield and concentration. [ABSTRACT FROM AUTHOR]

Surgery triggers a systemic inflammatory response that ultimately impacts the brain and associates with long-term cognitive impairment. Adequate regulation of this immune surge is pivotal for a successful surgical recovery. We explored the temporal immune response in a surgical cohort and its associations with neuroimmune regulatory pathways and cognition, in keeping with the growing body of evidence pointing towards the brain as a regulator of peripheral inflammation. Brain-to-immune communication acts through cellular, humoral and neural pathways. In this context, the vagal nerve and the cholinergic anti-inflammatory pathway (CAP) have been shown to modify peripheral immune cell activity in both acute and chronic inflammatory conditions. However, the relevance of neuroimmune regulatory mechanisms following a surgical trauma is not yet elucidated. Twenty-five male patients undergoing elective laparoscopic abdominal surgery were included in this observational prospective study. Serial blood samples with extensive immune characterization, assessments of heart rate variability (HRV) and cognitive tests were performed before surgery and continuing up to 6 months post-surgery. Temporal immune responses revealed biphasic reaction patterns with most pronounced changes at 5 hours after skin incision and 14 days following surgery. Estimations of cardiac vagal nerve activity through HRV recordings revealed great individual variations depending on the pre-operative HRV baseline. A principal component analysis displayed distinct differences in systemic inflammatory biomarker trajectories primarily based on preoperative HRV, with potiential consequences for long-term surgical outcomes. In conclusion, individual pre-operative HRV generates differential response patterns that associate with distinct inflammatory trajectories following surgery. Long-term surgical outcomes need to be examined further in larger studies with mixed gender cohorts. [ABSTRACT FROM AUTHOR]

On 6–8 June 2015, the Ion and Electron Sensor on board Rosetta observed keV‐range water‐group pickup ions arriving from the solar direction. Based on magnetic field intensification and variations, the appearance of the ions was likely to have been caused by a coronal mass ejection. During the 3‐day period when Rosetta was 200 km from the comet, peak ion energy/charge (E/q) varied over a range from 50 eV to 1 keV in concert with neutral gas density variations caused by the rotation of the comet and its variable solar illumination. Thermal ion densities showed the same variations. The neutral density variations provided a unique opportunity to observe the repeated slowing of the solar wind by mass loading caused by charge exchange between energetic water‐group ions and thermal water‐group molecules. Such solar wind slowing was observed previously only by flyby missions that provided single events. Plain Language Summary: The Rosetta orbiter carried a number of instruments to measure the properties of the neutral and ionized gas surrounding the nucleus. Included in these were plasma instruments to measure the characteristics of the charged particles. The Ion and Electron Sensor was one of them. Also on board were the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis, the Ion Composition Analyzer, and the Langmuir Probe. This paper discusses some of the results of measurements by these instruments and their relation to each other. It was found that the neutral gas emitted by the comet nucleus and the resulting positively charged ions interact in such a way to produce slowing down of the solar wind as a result of what is called "charge exchange", in which an electron is transferred from a neutral molecule to an ion. Key Points: Charge exchange of energetic water group pickup ions with coma water molecules is observed within the solar wind cavity of Comet 67P Churyumov‐GerasimenkoRotation of the comet produced variations in the neutral density at the spacecraft causing strong charge‐exchange deceleration of the incoming ions within the density peaksRecovery to the initial water‐group ion beam as minimum neutral densities, again appeared, was shown to result from pickup of thermal ions in the coma [ABSTRACT FROM AUTHOR]

Moment analysis of ion spectrograms measured by the Ion Composition Analyser (ICA) in the coma of comet 67P typically produces an ion number density estimate markedly lower than the number density of free electrons as measured by the Mutual Impedance Probe and the dual Langmuir Probe. While there are good reasons to distrust the ion density moment estimate in these circumstances, the issue cannot yet be considered fully understood and it is of interest to see whether any natural non-instrumental cause is possible. An obvious such cause would be whether a significant fraction of the positive charge density resides in positively charged dust grains that are not measured by the ICA. Here, we show that this scenario is highly unlikely, even near perihelion where photoemission is the strongest. In our semi-analytical grain charging model, we balance the current contributions to grains of photoelectron emission and electron attachment so as to find the expected charge state for a grain of a given radius. The charge state is affected by the ambient electron number density, the electron temperature, and the heliocentric distance. While at times the bulk of the dust population around comet 67P could be charged positive, dust charging, including photoelectron emission, should have a negligible influence on the overall ionization balance in the cometary coma simply because the dust particles are not ubiquitous enough. [ABSTRACT FROM AUTHOR]

The co-existence of bacteria and protozoa in aquatic environments has led to the evolution of predation defense mechanisms by the bacteria. Some of the predation-resistant bacteria (PRB) are also pathogenic to humans and other mammals. The links between PRB and protozoa in natural aquatic systems are poorly known, but they are important in predicting outbreaks and determining the long-term consequences of a contamination event. To elucidate co-occurrence patterns between PRB (16S rRNA) and bacterivorous protozoa (18S rRNA), we performed a field study in a coastal area in the northern Baltic Sea. Interactions between bacteria and protozoa were explored by using two complementary statistical tools. We found co-occurrence patterns between specific PRB and protozoa, such as Legionella and Ciliophora, and we also found that the interactions are genotype-specific as, for example, Rickettsia. The PRB sequence diversity was larger in bays and freshwater inlets compared to offshore sites, indicating local adaptions. Considering the PRB diversity in the freshwater in combination with the large spring floods in the area, freshwater influxes should be considered a potential source of PRB in the coastal northern Baltic Sea. These findings are relevant for the knowledge of survival and dispersal of potential pathogens in the environment. [ABSTRACT FROM AUTHOR]

Background: Apnoeic oxygenation using Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) during general anaesthesia prolongs the safe apnoeic period. However, there is a gap of knowledge how THRIVE‐induced hyperoxia and hypercapnia impact vital organs. The primary aim of this randomised controlled trial was to characterise oxidative stress and, secondary, vital organ function biomarkers during THRIVE compared to mechanical ventilation (MV). Methods: Thirty adult patients, American Society of Anesthesiologists (ASA) 1–2, undergoing short laryngeal surgery under general anaesthesia were randomised to THRIVE, FIO2 1.0, 70 L min−1 during apnoea or MV. Blood biomarkers for oxidative stress, malondialdehyde and TAC and vital organ function were collected (A) preoperatively, (B) at procedure completion and (C) at PACU discharge. Results: Mean apnoea time was 17.9 (4.8) min and intubation to end‐of‐surgery time was 28.1 (12.8) min in the THRIVE and MV group, respectively. Malondialdehyde increased from 11.2 (3.1) to 12.7 (3.1) µM (P =.02) and from 9.5 (2.2) to 11.6 (2.6) µM (P =.003) (A to C) in the THRIVE and MV group, respectively. S100B increased from 0.05 (0.02) to 0.06 (0.02) µg L−1 (P =.005) (A to C) in the THRIVE group. No increase in TAC, CRP, leukocyte count, troponin‐T, NTproBNP, creatinine, eGFRcrea or NSE was demonstrated during THRIVE. Conclusion: While THRIVE and MV was associated with increased oxidative stress, we found no change in cardiac, inflammation or kidney biomarkers during THRIVE. Further evaluation of stress and inflammatory response and cerebral and cardiac function during THRIVE is needed. [ABSTRACT FROM AUTHOR]

Wakes behind spacecraft caused by supersonic drifting positive ions are common in plasmas and disturb in situ measurements. We review the impact of wakes on observations by the Electric Field and Wave double‐probe instruments on the Cluster satellites. In the solar wind, the equivalent spacecraft charging is small compared to the ion drift energy and the wake effects are caused by the spacecraft body and can be compensated for. We present statistics of the direction, width, and electrostatic potential of wakes, and we compare with an analytical model. In the low‐density magnetospheric lobes, the equivalent positive spacecraft charging is large compared to the ion drift energy and an enhanced wake forms. In this case observations of the geophysical electric field with the double‐probe technique becomes extremely challenging. Rather, the wake can be used to estimate the flux of cold (eV) positive ions. For an intermediate range of parameters, when the equivalent charging of the spacecraft is similar to the drift energy of the ions, also the charged wire booms of a double‐probe instrument must be taken into account. We discuss an example of these effects from the MMS spacecraft near the magnetopause. We find that many observed wake characteristics provide information that can be used for scientific studies. An important example is the enhanced wakes used to estimate the outflow of ionospheric origin in the magnetospheric lobes to about 1026 cold (eV) ions/s, constituting a large fraction of the mass outflow from planet Earth. Plain Language Summary: Wakes caused by spacecraft motion or drifting plasma are common behind spacecraft with scientific instruments and disturb in situ observations of space plasmas. We review the impact of wakes on observations by the Electric Field and Wave double‐probe instruments on the Cluster satellites. In the solar wind, the wake behind a Cluster spacecraft is caused by the spacecraft body, is narrow, and can partly be compensated for when analyzing data. In the regions above the Earth's polar regions, the wake behind a Cluster spacecraft is caused by an electrostatic structure around the positively charged spacecraft, causing an enhanced wake. The charging stops positive ions from reaching the spacecraft. Rather, this wake can be used to estimate the flux of cold (eV) positive ions escaping from the ionosphere. Above the poles the flux is about 1026 ions/s, constituting a large fraction of the mass outflow from planet Earth. For an intermediate range of parameters, when the drift energy of the ions is comparable to the equivalent charge of the spacecraft, also the charged wire booms of a double‐probe instrument must be taken into account. We discuss an example from the MMS spacecraft near the magnetopause. Key Points: Plasma wakes are common behind scientific spacecraftWakes in the solar wind can be compensated for in data analysisEnhanced wakes in the polar lobes can be used to detect cold outflowing ions [ABSTRACT FROM AUTHOR]

Background: Individuals with type 1 diabetes have a markedly increased risk of stroke. In the general population, genetic predisposition has been linked to increased risk of stroke, but this has not been assessed in type 1 diabetes. Our aim was, therefore, to study how parental risk factors affect the risk of stroke in individuals with type 1 diabetes. Methods: This study represents an observational follow-up of 4011 individuals from the Finnish Diabetic Nephropathy Study, mean age at baseline 37.6 ± 11.9 years. All strokes during follow-up were verified from medical records or death certificates. The strokes were classified as either ischemic or hemorrhagic. All individuals filled out questionnaires concerning their parents' medical history of hypertension, diabetes, stroke, and/or myocardial infarction. Results: During a median follow-up of 12.4 (10.9–14.2) years, 188 individuals (4.6%) were diagnosed with their first ever stroke; 134 were ischemic and 54 hemorrhagic. In Cox regression analysis, a history of maternal stroke increased the risk of hemorrhagic stroke, hazard ratio 2.86 (95% confidence interval 1.27–6.44, p = 0.011) after adjustment for sex, age, BMI, retinal photocoagulation, and diabetic kidney disease. There was, however, no association between maternal stroke and ischemic stroke. No other associations between parental risk factors and ischemic or hemorrhagic stroke were observed. Conclusion: A history of maternal stroke increases the risk of hemorrhagic stroke in individuals with type 1 diabetes. Other parental risk factors seem to have limited impact on the risk of stroke. [ABSTRACT FROM AUTHOR]

Objectives: Humoral and cellular immunity to SARS‐CoV‐2 following COVID‐19 will likely contribute to protection from reinfection or severe disease. It is therefore important to characterise the initiation and persistence of adaptive immunity to SARS‐CoV‐2 amidst the ongoing pandemic. Methods: Here, we conducted a longitudinal study on hospitalised moderate and severe COVID‐19 patients from the acute phase of disease into convalescence at 5 and 9 months post‐symptom onset. Utilising flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune responses during and after human SARS‐CoV‐2 infection. Results: During acute COVID‐19, we observed an increase in germinal centre activity, a substantial expansion of antibody‐secreting cells and the generation of SARS‐CoV‐2‐neutralising antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralising antibody titres as well as robust specific memory B cell responses and polyfunctional T cell responses at 5 and 9 months after symptom onset in both moderate and severe COVID‐19 patients. Conclusion: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS‐CoV‐2‐specific immunological memory in hospitalised COVID‐19 patients long after recovery, likely contributing towards protection against reinfection. [ABSTRACT FROM AUTHOR]

Purpose: To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. Methods: Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. Results: Both regions examined, IR and UIR, exhibited over weeks 1–17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. Conclusion: This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometryanalysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-line-age-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19. [ABSTRACT FROM AUTHOR]

Background: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID‐19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID‐19 admitted to ICU. Methods: We included all 260 patients with COVID‐19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in‐hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. Results: Of 260 ICU patients with COVID‐19, 208 (80.0%) were men, the median age was 59 (IQR 51‐65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8‐14) days. Sixty‐two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6‐18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. Conclusion: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID‐19 admitted to ICU in a large tertiary hospital in Sweden. [ABSTRACT FROM AUTHOR]

We report the detection of large‐amplitude, quasi‐harmonic density fluctuations with associated magnetic field oscillations in the region surrounding the diamagnetic cavity of comet 67P. Typical frequencies are ∼0.1 Hz, corresponding to ∼10 times the water and ≲0.5 times the proton gyro‐frequencies, respectively. Magnetic field oscillations are not always clearly observed in association with these density fluctuations, but when they are, they consistently have wave vectors perpendicular to the background magnetic field, with the principal axis of polarization close to field‐aligned and with a ∼90° phase shift with respect to the density fluctuations. The fluctuations are observed in association with asymmetric plasma density and magnetic field enhancements previously found in the region surrounding the diamagnetic cavity, occurring predominantly on their descending slopes. This is a new type of waves not previously observed at comets. They are likely ion Bernstein waves, and we propose that they are excited by unstable ring, ring‐beam, or spherical shell distributions of cometary ions just outside the cavity boundary. These waves may play an important role in redistributing energy between different particle populations and reshape the plasma environment of the comet. Key Points: Large‐amplitude low‐frequency (around 0.1 Hz) plasma density fluctuations are observed at comet 67PThey coincide with the plasma density and magnetic field enhancements surrounding the diamagnetic cavityThis is a new type of waves at comets, probably ion Bernstein waves, possibly driven by velocity space anisotropies arising near the cavity [ABSTRACT FROM AUTHOR]

Objectives: The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is unknown. Understanding the immune response in COVID‐19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID‐19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID‐19. Methods: Blood samples collected from moderately (n = 11) and severely ill (n = 12) COVID‐19 patients, as well as healthy control donors (n = 16), were analysed with 18‐parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID‐19 patients, and serum biomarkers were analysed with multiplex immunoassays. Results: Innate lymphoid cells were largely depleted from the circulation of COVID‐19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID‐19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID‐19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion: This study provides insights into the potential role of ILCs in immune responses against SARS‐CoV‐2, particularly linked to the severity of COVID‐19. [ABSTRACT FROM AUTHOR]

Average flow patterns of ions around comet 67P detected by the RPC-ICA instrument onboard Rosetta are presented both as a time series and as a spatial distribution of the average flow in the plane perpendicular to the comet – Sun direction (Y–Z plane in the coordinate systems used). Cometary ions in the energy range up to 60 eV flow radially away from the nucleus in the Y–Z plane, irrespective of the direction of the magnetic field, throughout the mission. These ions may however be strongly affected by the spacecraft potential, the uncertainty due to this is briefly discussed. Inside the solar wind ion cavity and in the periods just before and after, the cometary pick up ions moving antisunward are deflected against the inferred solar wind electric field direction. This is opposite to what is observed for lower levels of mass-loading. These pick up ions are behaving in a similar way to the solar wind ions and are deflected due to mass-loading. A spatial asymmetry can be seen in the observations of deflected pick up ions, with motion against the electric field primarily within a radius of 200 km of the nucleus and also in the negative electric field hemisphere. Cometary ions observed by RPC-ICA typically move in the antisunward direction throughout the mission. These are average patterns, full-resolution data show very much variability. [ABSTRACT FROM AUTHOR]

Background: Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) using high‐flow 100% oxygen during apnoea has gained increased use during difficult airway management and laryngeal surgery due to a slower carbon dioxide rise compared to traditional apnoeic oxygenation. We have previously demonstrated high arterial oxygen partial pressures and an increasing arterial‐alveolar carbon dioxide difference during THRIVE. Primary aim of this study was to characterise lung volume changes measured with electrical impedance tomography during THRIVE compared to mechanical ventilation. Methods: Thirty adult patients undergoing laryngeal surgery under general anaesthesia were randomised to THRIVE or mechanical ventilation. Subjects were monitored with electrical impedance tomography and repeated blood gas measurement perioperatively. The THRIVE group received 100% oxygen at 70 l min−1 during apnoea. The mechanical ventilation group was intubated and normoventilated with an FiO2 of 0.4. Results: Mean age were 48.2 (19.9) and 51.3 (12.3) years, and BMI 26.0 (4.5) and 26.0 (3.9) in the THRIVE and mechanical ventilation group respectively. Mean apnoea time in the THRIVE group was 17.9 (4.8) min. Mean apnoea to end‐of‐surgery time was 28.1 (12.8) min in the mechanical ventilation group. No difference in delta End Expiratory Lung Impedance was seen between groups over time. In the THRIVE group all but three subjects were well oxygenated during apnoea. THRIVE was discontinued for the three patients who desaturated. Conclusions: No difference in lung volume change over time, measured by electrical impedance tomography, was detected when using THRIVE compared to mechanical ventilation during laryngeal surgery. [ABSTRACT FROM AUTHOR]

Context. The electrostatic potential of a spacecraft, VS, is important for the capabilities of in situ plasma measurements. Rosetta has been found to be negatively charged during most of the comet mission and even more so in denser plasmas. Aims. Our goal is to investigate how the negative VS correlates with electron density and temperature and to understand the physics of the observed correlation. Methods. We applied full mission comparative statistics of VS, electron temperature, and electron density to establish VS dependence on cold and warm plasma density and electron temperature. We also used Spacecraft-Plasma Interaction System (SPIS) simulations and an analytical vacuum model to investigate if positively biased elements covering a fraction of the solar array surface can explain the observed correlations. Results. Here, the VS was found to depend more on electron density, particularly with regard to the cold part of the electrons, and less on electron temperature than was expected for the high flux of thermal (cometary) ionospheric electrons. This behaviour was reproduced by an analytical model which is consistent with numerical simulations. Conclusions. Rosetta is negatively driven mainly by positively biased elements on the borders of the front side of the solar panels as these can efficiently collect cold plasma electrons. Biased elements distributed elsewhere on the front side of the panels are less efficient at collecting electrons apart from locally produced electrons (photoelectrons). To avoid significant charging, future spacecraft may minimise the area of exposed bias conductors or use a positive ground power system. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Are carotid bodies (CBs) modulated by the damage‐associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury?What are the main findings and their importance?DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF‐α from ex vivo rat CBs. All‐thiol HMGB1 mediates upregulation of immune‐related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity. The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen‐associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger‐associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all‐thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all‐thiol HMGB1‐driven upregulation of a number of prominent pro‐inflammatory markers including Il1α and Il1β. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune‐related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity. [ABSTRACT FROM AUTHOR]

Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis. [ABSTRACT FROM AUTHOR]

We calculate the momentum flux and pressure of ions measured by the Ion Composition Analyzer (ICA) on the Rosetta mission at comet 67P/Churyumov‐Gerasimenko. The total momentum flux stays roughly constant over the mission, but the contributions of different ion populations change depending on heliocentric distance. The magnetic pressure, calculated from Rosetta magnetometer measurements, roughly corresponds with the cometary ion momentum flux. When the spacecraft enters the solar wind ion cavity, the solar wind fluxes drop drastically, while the cometary momentum flux becomes roughly 10 times the solar wind fluxes outside of the ion cavity, indicating that pickup ions behave similarly to the solar wind ions in this region. We use electron density from the Langmuir probe to calculate the electron pressure, which is particularly important close to the comet nucleus where flow changes from antisunward to radially outward. Plain Language Summary: To understand the atmosphere of a comet, we must understand how its charged particles interact with the solar wind. Here we look at momentum flux, the amount of momentum carried by particles flowing through a certain area, measured at the comet 67P/Churyumov‐Gerasimenko by the Rosetta spacecraft. We find that the total momentum flux changes the amount we would expect from the comet getting closer to the Sun. When in the part of the atmosphere with no solar wind, the ions coming from the comet have more momentum flux than the solar wind ions elsewhere in the comet atmosphere. The increase matches what we expect from the comet getting closer to the Sun, which increases the total density of the comet atmosphere. The cometary ions replace the solar wind ions in the atmosphere, so the total stays the same. The magnetic field varies with the cometary ions. We find electron pressure with measured electron data. It is higher than the momentum flux, especially in the part of the atmosphere close to the comet nucleus. This means that the atmosphere here is primarily moving outward from the comet, while farther away from the nucleus it is mainly flowing away from the Sun. Key Points: Momentum flux of Rosetta ion data shows the evolution of a cometary ionosphere, including boundary regionsMagnetic pressure is on the order of the total ion momentum flux and roughly corresponds with cometary ion momentum fluxThe cometary pickup ions in the solar wind ion cavity take over the role of the solar wind ions outside the cavity [ABSTRACT FROM AUTHOR]

Activated NK cells in severe COVID-19: Natural killer (NK) cells are cytotoxic lymphocytes that provide innate immune defense against viral infections and cancer, but little is known about their involvement in the host response to COVID-19. Maucourant et al. used high-dimensional flow cytometry to characterize NK cells in patients with moderate or severe COVID-19. SARS-CoV-2 infection was associated with fewer blood NK cells but a higher activation state in circulating NK cells. Severe COVID-19 resulted in an increase in "armed" NK cells containing high levels of cytotoxic proteins such as perforin. The adaptive NK subset was markedly expanded in a subset of severe patients. These findings lay the groundwork for future studies examining the mechanisms of NK cell activation in COVID-19 and their potential roles in host protection and immunopathology. Understanding innate immune responses in coronavirus disease 2019 (COVID-19) is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in single-cell RNA sequencing signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Last, arming of CD56bright NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease. [ABSTRACT FROM AUTHOR]

Objective: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery.Methods: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively.Results: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio).Interpretation: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected. [ABSTRACT FROM AUTHOR]

Context: The Knee Self-Efficacy Scale (K-SES) has good reliability, validity, and responsiveness for patients' perceived knee-function self-efficacy during rehabilitation after an anterior cruciate ligament (ACL) injury. Preoperative knee-function self-efficacy has also been shown to have a predictive ability in terms of outcome 1 y after ACL reconstruction. Objective: To evaluate a new clinical rehabilitation model containing strategies to enhance knee-function selfefficacy. Design: A randomized, controlled study. Setting: Rehabilitation clinic and laboratory. Patients: 40 patients with ACL injuries. Intervention: All patients followed a standardized rehabilitation protocol. Patients in the experimental group were treated by 1 of 3 physiotherapists who had received specific training in a clinical rehabilitation model. These physiotherapists were also given their patients' self-efficacy scores after the initial and 4-, 6-, and 12-mo follow-ups, whereas the 5 physiotherapists treating the patients in the control group were not given their patients' self-efficacy scores. Main Outcome Measures: The K-SES, the Tegner Activity Scale, the Physical Activity Scale, the Knee Injury and Osteoarthritis Outcome Score, and the Multidimensional Health Locus of Control. Results: Twenty-four patients (12 in each group) completed all followups. Current knee-function self-efficacy, knee symptoms in sports, and knee quality of life improved significantly (P = .05) in both groups during rehabilitation. Both groups had a significantly (P = .05) lower physical activity level at 12 mo than preinjury. No significant differences were found between groups. Conclusion: In this study there was no evidence that the clinical rehabilitation model with strategies to enhance self-efficacy resulted in a better outcome than the rehabilitation protocol used for the control group. [ABSTRACT FROM AUTHOR]

Introduction In the early weeks after surgery, patients may experience cognitive changes and impaired memory and concentration—changes commonly referred to as postoperative cognitive decline. It is often the patient and/ or a relative that initially detects a change in cognitive capacity after surgery, typically when resuming daily activities. We lack information about how patients experience early postoperative cognition (delayed neurocognitive recovery) and if these experiences can be reflected in biochemical pattern of inflammatory signalling molecules, cognitive function as well as on quality of postoperative recovery. Methods and analysis The study has a mixed-methods design that is integration of qualitative and quantitative data within a single investigation. Participants included will be patients aged ≥60 years that are undergoing major elective joint replacement surgery (n=40) and their relative. Patient’s experience of his/her early cognition will be captured by interviews on postoperative day 13–16 during the follow-up visit. A relative will also be interviewed on the same day or the day after. Cognitive function will be measured preoperatively and on postoperative day 13–16 using the International Study Group of Postoperative Cognitive Dysfunction test battery. Symptoms/discomfort will be measured preoperatively and postoperatively (on postoperative day 1 and 2 and at the follow-up visit day 13–16) by the Swedish version of Quality of Recovery and by a visual analogue scale assessing pain intensity. Biomarkers will also be collected at the same time points. The findings from the interviews will be sorted out depending on group stratification (no delayed neurocognitive recovery and delayed neurocognitive recovery). The qualitative and quantitative findings will be compared to seek for similarities and differences. Ethics and dissemination The project has been approved by the Swedish Ethical Review Authority (2019–02968) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, scientific conferences and in social media. [ABSTRACT FROM AUTHOR]

We present the electron density (ne) altitude profiles of Saturn's ionosphere at near‐equatorial latitudes from all 23 orbits of Cassini's Grand Finale. The data are collected by the Langmuir probe part of the Radio and Plasma Wave Science investigation. A high degree of variability in the electron density profiles is observed. However, organizing them by consecutive altitude ranges revealed clear differences between the southern and northern hemispheres. The ne profiles are shown to be more variable and connected to the D‐ring below 5,000 km in the southern hemisphere compared to the northern hemisphere. This observed variability is explained to be a consequence of an electrodynamic interaction with the D‐ring. Moreover, a density altitude profile is constructed for the northern hemisphere indicating the presence of three different ionospheric layers. Similar properties were observed during Cassini's final plunge, where the main ionospheric peak is crossed at ∼1,550‐km altitude. Plain Language Summary: The Cassini Langmuir probe measured directly the uppermost layer of Saturn's atmosphere, the ionosphere, during its Grand Finale. The observations revealed a layered electron density altitude profile with evidence in the southern hemisphere of an electrodynamic type of interaction with the planet innermost D‐ring. Moreover, the main peak of the ionosphere is observed for the first time in the final plunge around 1,550 km. Key Points: Cassini RPWS observations during the Grand Finale show an electrodynamic type of interaction between the topside ionosphere and the D‐ring in the southern hemisphereA layered electron density profile is observed, characterized by at least a diffusive and a chemical equilibrium regionThe main ionospheric peak is observed around 1,550 km in the final plunge [ABSTRACT FROM AUTHOR]

Background: Although the use of thromboprophylaxis is well established, there is no consensus on the preferred thromboprophylaxis regimen after THA; large, population-based studies offer an opportunity to examine this problem in a robust way that can complement results from randomized trials.Questions/purposes: Using data from a large national registry, we asked: (1) Is there any difference between low-molecular weight heparin (LMWH) and new oral anticoagulants in preventing symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), after THA? (2) Are there any differences in safety parameters, such as bleeding, reoperations and mortality, between LMWH and new oral anticoagulants?Methods: Between 2008 and 2012, 78,066 THAs were performed in Sweden. This study evaluated 32,663 (42%) of them, selected through the merger of several national registries. These patients underwent unilateral THA due to primary osteoarthritis. They had not experienced any venous thromboembolic events 5 years before the index operation and were not prescribed potent antithrombotic agents, of any type, in the 6 months before the index operation. Additionally, their postoperative thromboprophylaxis was confirmed in a national registry by purchase of prescribed medications. We divided the cohort into two groups: those patients who received new oral anticoagulants (5752, 18%) and those who received LMWH (26,881, 82%) as postoperative thromboprophylaxis. Our primary endpoints were the frequencies of symptomatic DVT and symptomatic PE within 3 months of surgery. Our secondary comparison was a between-group comparison of bleeding (by way of diagnostic coding), reoperation, and mortality within 3 months of surgery. Odds ratios (OR) are presented with 95% confidence intervals (CIs) as pooled results for the two groups after adjustment for duration of thromboprophylaxis (short or extended for at least 28 days), year of the index operation, Elixhauser comorbidity index, sex, age and previous treatment with platelet aggregation inhibitors.Results: The risk of symptomatic DVT was lower in the group that received new oral anticoagulants than the group that received LMWH (0.3% versus 0.6%, OR, 0.47; 95% CI, 0.27-0.76; p = 0.026). The risk of symptomatic PE was lower in the group that received new oral anticoagulants than the group that received LMWH (0.1% versus 0.4%, OR, 0.36; 95% CI, 0.16-0.69; p = 0.005). There was no difference in the risk of bleeding (by way of diagnostic coding) (OR, 1.03; 95% CI, 0.82-1.28; p = 0.688), reoperation (OR, 1.02; 95% CI, 0.71-1.44; p = 0.860) or mortality (OR, 0.83; 95% CI, 0.31-1.88; p = 0.883) between groups.Conclusions: New oral anticoagulants were associated with a lower risk of symptomatic DVT and symptomatic PE in this large, registry study, and we observed no differences in the risk of bleeding, reoperation, or death between the groups. Although we were able to control for a number of potential confounding variables, we cannot ascertain the indications that drove the prescription decisions in this setting, and there were important between-group differences in terms of duration of thromboprophylaxis (new oral anticoagulants generally were used for a longer period of time after surgery). Future studies, preferably large randomized trials with pragmatic inclusion criteria, to analyze symptomatic DVT, symptomatic PE and death are needed to confirm or refute our findings.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Measurements of electrons and ions in Saturn's ionosphere down to 1,500‐km altitudes as well as the ring crossing region above the ionosphere obtained by the Langmuir probe onboard the Cassini spacecraft are presented. Five nearly identical deep ionosphere flybys during the Grand Finale orbits and the Final plunge orbit revealed a rapid increase in the plasma densities and discrepancies between the electrons and ions densities (Ne and Ni) near the closest approach. The small Ne/Ni ratio indicates the presence of a dusty plasma, a plasma which charge carrier is dominated by negatively charged heavy particles. Comparison of the Langmuir probe obtained density with the light ion density obtained by the Ion and Neutral Mass Spectrometer confirmed the presence of heavy ions. An unexpected positive floating potential of the probe was also observed when Ne/Ni ≪ 1. This suggests that Saturn's ionosphere near the density peak is in a dusty plasma state consisting of negatively and positively charged heavy cluster ions. The electron temperature (Te) characteristics in the ionosphere are also investigated and unexpectedly high electron temperature value, up to 5000 K, has been observed below 2,500‐km altitude in a region where electron‐neutral collisions should be prominent. A well‐defined relationship between Te and Ne/Ni ratio was found, implying that the electron heating at low altitudes is related to the dusty plasma state of the ionosphere. Plain Language Summary: Cassini Langmuir probe measurements revealed ion densities in excess of the electron densities, indicative of a dusty plasma, in Saturn's ionosphere below 2,500‐km altitude. Comparison of the Langmuir probe measurements with those of the Ion and Neutral Mass Spectrometer, sensitive to only lighter ions during this period, showed that heavy ions dominate in this region. Positive spacecraft potentials were also found, suggesting that Saturn's ionosphere contains dusty plasma of negatively and positively charged heavy ions. Key Points: In situ measurements of Saturn's ionospheric plasma densities down to 1,500 km and the ring above the ionosphere is presentedCharge imbalance in the ions and electrons, evidence of the negatively charged heavy particles, has been observed below 2,500 kmObservations suggest that Saturn's ionosphere consists of a significant amount of negatively and positively charged heavy ions [ABSTRACT FROM AUTHOR]

In a cometary coma, the ion-neutral decoupling distance, sometimes referred to as the ion exobase or collisionopause, can be defined as the cometocentric distance, r in, where ions, initially moving with the neutral outgassing speed, have a probability of 1/ e of not colliding with neutrals on their subsequent journey radially outwards. We present an analytical model for calculating this decoupling distance in the presence of a static radial electric field. We show that for a logarithmically decaying potential, the value of r incan even decrease to ∼15 per cent of its field-free case value. Moreover, already at this distance, the effective ion speed can be expected to markedly exceed the neutral expansion velocity. These analytical results are in line with previous numerical calculations, adapting similar but not identical field profiles. The presence of a non-negligible ambipolar electric field and limited importance of ion-neutral collisional coupling are further supported by observations in the diamagnetic cavity of comet 67P/Churyumov–Gerasimenko by plasma instruments onboard Rosetta that reveal ion speeds several times higher than the neutral expansion velocity. [ABSTRACT FROM AUTHOR]

The article focuses on nocturnal blood pressure has associated with cerebral small-vessel disease in type 1 diabetes. Topics inlcude the vascular complications are a hallmark of diabetes, the cerebral small-vessel disease (cSVD) in type 1 diabetes remains scarcely studied, and the cSVD is more common in individuals with type 1 diabetes than healthy control subjects and has associated with systolic office blood pressure.

The spacecraft potential is often used to infer rapid changes in the thermal plasma density. The variations in spacecraft potential associated with large‐amplitude Langmuir and upper hybrid waves are investigated with the Magnetospheric Multiscale (MMS) mission. When large‐amplitude Langmuir and upper hybrid waves are observed, the spacecraft potential increases. The changes in spacecraft potential are shown to be due to enhanced photoelectron escape from the spacecraft when the wave electric fields reach large amplitude. The fluctuations in spacecraft potential follow the envelope function of the Langmuir and upper hybrid waves. Comparison with the high‐resolution electron moments shows that the changes in spacecraft potential associated with the waves are not due to density perturbations. Indeed, using the spacecraft potential as a density probe leads to unphysically large density fluctuations. In addition, the changes in spacecraft potential are shown to increase as density decreases: larger spacecraft potential changes are observed in the magnetosphere, than in the magnetosheath and solar wind. These results show that external electric fields can lead to unphysical results when the spacecraft potential is used as a density probe. The results suggest that fluctuations in the spacecraft potential alone cannot be used to determine whether nonlinear processes associated with Langmuir and upper hybrid waves, such as the ponderomotive force and three‐wave decay, are occurring. Key Points: The electric field of Langmuir and upper hybrid waves increases the spacecraft potential due to enhanced photoelectron escapeIncreased spacecraft potentials associated with Langmuir and upper hybrid waves are not due to density depletions or ponderomotive forceThe magnitude of the changes in spacecraft potential due to Langmuir and upper hybrid waves becomes larger as density decreases [ABSTRACT FROM AUTHOR]

Abstract: A major point of interest in cometary plasma physics has been the diamagnetic cavity, an unmagnetized region in the innermost part of the coma. Here we combine Langmuir and Mutual Impedance Probe measurements to investigate ion velocities and electron temperatures in the diamagnetic cavity of comet 67P, probed by the Rosetta spacecraft. We find ion velocities generally in the range 2–4 km/s, significantly above the expected neutral velocity ≲1 km/s, showing that the ions are (partially) decoupled from the neutrals, indicating that ion‐neutral drag was not responsible for balancing the outside magnetic pressure. Observations of clear wake effects on one of the Langmuir probes showed that the ion flow was close to radial and supersonic, at least with respect to the perpendicular temperature, inside the cavity and possibly in the surrounding region as well. We observed spacecraft potentials ≲ − 5 V throughout the cavity, showing that a population of warm (∼5 eV) electrons was present throughout the parts of the cavity reached by Rosetta. Also, a population of cold ( ≲ 0 . 1 eV) electrons was consistently observed throughout the cavity, but less consistently in the surrounding region, suggesting that while Rosetta never entered a region of collisionally coupled electrons, such a region was possibly not far away during the cavity crossings. [ABSTRACT FROM AUTHOR]

We present a Rosetta Plasma Consortium (RPC) case study based on four events in 2015 autumn at various radial distances, phase angles and local times, just after the perihelion of comet 67P/Churyumov-Gerasimenko. Pulse-like (high-amplitude, up to minutes in time) signatures are seen with several RPC instruments in the plasma density (with the LAngmuir Probe, LAP and Mutual Impedance Probe, MIP), ion energy and flux (with the Ion Composition Analyzer, ICA) and the magnetic field intensity (with the magnetometer, MAG). Furthermore, the cometocentric distance relative to the electron exobase is seen to be a good organizing parameter for the measured plasma variations. The closer Rosetta is to this boundary, the more pulses are measured. This is consistent with the pulses being filaments of plasma originating from the diamagnetic cavity boundary, as predicted by simulations. [ABSTRACT FROM AUTHOR]