Individual and collective behavior of dust particles in a protoplanetary nebula

We study the interaction between gas and dust particles in a protoplanetary disk, comparing analytical and numerical results. We first calculate analytically the trajectories of individual particles undergoing gas drag in the disk, in the asymptotic cases of very small particles (Epstein regime) and very large particles (Stokes regime). Using a Boltzmann averaging method, we then infer their collective behavior. We compare the results of this analytical formulation against numerical computations of a large number of particles. Using successive moments of the Boltzmann equation, we derive the equivalent fluid equations for the average motion of the particles; these are intrinsically different in the Epstein and Stokes regimes. We are also able to study analytically the temporal evolution of a collection of particles with a given initial size-distribution provided collisions are ignored.Comment: 15 pages, 9 figures, submitted to Ap

Dust Distribution in Gas Disks. A Model for the Ring Around HR 4796A

There have been several model analyses of the near and mid IR flux from the circumstellar ring around HR4796A. In the vicinity of a young star, the possibility that the dust ring is embedded within a residual protostellar gas disk cannot be ruled out. In a gas-rich environment, larger sizes ($>100 \mu m$) are needed for the particles to survive the radiative blow out. The total dust mass required to account for the IR flux is $< 10^{-1} M_\oplus$. The combined influence of gas and stellar radiation may also account for the observed sharp inner boundary and rapidly fading outer boundary of the ring. The pressure gradient induced by a small (10%) amplitude variation in the surface density distribution of a low-mass gaseous disk would be sufficient to modify the rotation speed of the gas.Comment: proof read version, 26 pages, LaTex, 11 figures. To appear in The Astronomical Journal June 200

Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool

BACKGROUND: Clinical trials aim to draw conclusions about the effects of treatments, but a trial can address many different potential questions. For example, does the treatment work well for patients who take it as prescribed? Or does it work regardless of whether patients take it exactly as prescribed? Since different questions can lead to different conclusions on treatment benefit, it is important to clearly understand what treatment effect a trial aims to investigate-this is called the 'estimand'. Using estimands helps to ensure trials are designed and analysed to answer the questions of interest to different stakeholders, including patients and public. However, there is uncertainty about whether patients and public would like to be involved in defining estimands and how to do so. Public partners are patients and/or members of the public who are part of, or advise, the research team. We aimed to (i) co-develop a tool with public partners that helps explain what an estimand is and (ii) explore public partner's perspectives on the importance of discussing estimands during trial design. METHODS: An online consultation meeting was held with 5 public partners of mixed age, gender and ethnicities, from various regions of the UK. Public partner opinions were collected and a practical tool describing estimands, drafted before the meeting by the research team, was developed. Afterwards, the tool was refined, and additional feedback sought via email. RESULTS: Public partners want to be involved in estimand discussions. They found an introductory tool, to be presented and described to them by a researcher, helpful for starting a discussion about estimands in a trial design context. They recommended storytelling, analogies and visual aids within the tool. Four topics related to public partners' involvement in defining estimands were identified: (i) the importance of addressing questions that are relevant to patients and public in trials, (ii) involving public partners early on, (iii) a need for education and communication for all stakeholders and (iv) public partners and researchers working together. CONCLUSIONS: We co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions

Surface Outflow in Optically Thick Dust Disks by the Radiation Pressure

We study the outflow of dust particles on the surface layers of optically thick disks. At the surface of disks around young stars, small dust particles (size < 10 micron) experience stellar radiation pressure support and orbit more slowly than the surrounding gas. The resulting tail-wind imparts energy and angular momentum to the dust particles, moving them outward. This outflow occurs in the thin surface layer of the disk that is exposed to starlight, and the outward mass flux is carried primarily by particles of size ~0.1 micron. Beneath the irradiated surface layer, dust particles experience a head-wind, which drives them inward. For the specific case of a minimum-mass-solar-nebula, less than a thousandth of the dust mass experiences outward flow. If the stellar luminosity is 15 times brighter than the sun, however, or if the gas disk mass is as small as ~100 M_earth, then the surface outflow can dominate the inward flux in certain radial ranges, leading to the formation of rings or gaps in the dust disks.Comment: 14 pages, 7 figures, ApJ accepte

Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool

Background: Clinical trials aim to draw conclusions about the effects of treatments, but a trial can address many different potential questions. For example, does the treatment work well for patients who take it as prescribed? Or does it work regardless of whether patients take it exactly as prescribed? Since different questions can lead to different conclusions on treatment benefit, it is important to clearly understand what treatment effect a trial aims to investigate—this is called the ‘estimand’. Using estimands helps to ensure trials are designed and analysed to answer the questions of interest to different stakeholders, including patients and public. However, there is uncertainty about whether patients and public would like to be involved in defining estimands and how to do so. Public partners are patients and/or members of the public who are part of, or advise, the research team. We aimed to (i) co-develop a tool with public partners that helps explain what an estimand is and (ii) explore public partner’s perspectives on the importance of discussing estimands during trial design. Methods: An online consultation meeting was held with 5 public partners of mixed age, gender and ethnicities, from various regions of the UK. Public partner opinions were collected and a practical tool describing estimands, drafted before the meeting by the research team, was developed. Afterwards, the tool was refined, and additional feedback sought via email. Results: Public partners want to be involved in estimand discussions. They found an introductory tool, to be presented and described to them by a researcher, helpful for starting a discussion about estimands in a trial design context. They recommended storytelling, analogies and visual aids within the tool. Four topics related to public partners’ involvement in defining estimands were identified: (i) the importance of addressing questions that are relevant to patients and public in trials, (ii) involving public partners early on, (iii) a need for education and communication for all stakeholders and (iv) public partners and researchers working together. Conclusions: We co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions

Immunomodulatory drugs in sepsis: a systematic review and meta-analysis

\ua9 2024 The Authors. Anaesthesia published by John Wiley &amp; Sons Ltd on behalf of Association of Anaesthetists. Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs

Cascades and Cognitive State: Focused Attention Incurs Subcritical Dynamics

The analysis of neuronal avalanches supports the hypothesis that the human cortex operates with critical neural dynamics. Here, we investigate the relationship between cascades of activity in electroencephalogram data, cognitive state, and reaction time in humans using a multimodal approach. We recruited 18 healthy volunteers for the acquisition of simultaneous electroencephalogram and functional magnetic resonance imaging during both rest and during a visuomotor cognitive task. We compared distributions of electroencephalogram-derived cascades to reference power laws for task and rest conditions. We then explored the large-scale spatial correspondence of these cascades in the simultaneously acquired functional magnetic resonance imaging data. Furthermore, we investigated whether individual variability in reaction times is associated with the amount of deviation from power law form. We found that while resting state cascades are associated with approximate power law form, the task state is associated with subcritical dynamics. Furthermore, we found that electroencephalogram cascades are related to blood oxygen level-dependent activation, predominantly in sensorimotor brain regions. Finally, we found that decreased reaction times during the task condition are associated with increased proximity to power law form of cascade distributions. These findings suggest that the resting state is associated with near-critical dynamics, in which a high dynamic range and a large repertoire of brain states may be advantageous. In contrast, a focused cognitive task induces subcritical dynamics, which is associated with a lower dynamic range, which in turn may reduce elements of interference affecting task performance

Tuberculosis in Dr Granville's mummy: a molecular re-examination of the earliest known Egyptian mummy to be scientifically examined and given a medical diagnosis

‘Dr Granville's mummy’ was described to the Royal Society of London in 1825 and was the first ancient Egyptian mummy to be subjected to a scientific autopsy. The remains are those of a woman, Irtyersenu, aged about 50, from the necropolis of Thebes and dated to about 600 BC. Augustus Bozzi Granville (1783–1872), an eminent physician and obstetrician, described many organs still in situ and attributed the cause of death to a tumour of the ovary. However, subsequent histological investigations indicate that the tumour is a benign cystadenoma. Histology of the lungs demonstrated a potentially fatal pulmonary exudate and earlier studies attempted to associate this with particular disease conditions. Palaeopathology and ancient DNA analyses show that tuberculosis was widespread in ancient Egypt, so a systematic search for tuberculosis was made, using specific DNA and lipid biomarker analyses. Clear evidence for Mycobacterium tuberculosis complex DNA was obtained in lung tissue and gall bladder samples, based on nested PCR of the IS6110 locus. Lung and femurs were positive for specific M. tuberculosis complex cell-wall mycolic acids, demonstrated by high-performance liquid chromatography of pyrenebutyric acid–pentafluorobenzyl mycolates. Therefore, tuberculosis is likely to have been the major cause of death of Irtyersenu

Mapping the sociodemographic distribution and self-reported justifications for non-compliance with COVID-19 guidelines in the United Kingdom

Which population factors have predisposed people to disregard government safety guidelines during the COVID-19 pandemic and what justifications do they give for this non-compliance? To address these questions, we analyse fixed-choice and free-text responses to survey questions about compliance and government handling of the pandemic, collected from tens of thousands of members of the UK public at three 6-monthly timepoints. We report that sceptical opinions about the government and mainstream-media narrative, especially as pertaining to justification for guidelines, significantly predict non-compliance. However, free text topic modelling shows that such opinions are diverse, spanning from scepticism about government competence and self-interest to full-blown conspiracy theories, and covary in prevalence with sociodemographic variables. These results indicate that attempts to counter non-compliance through argument should account for this diversity in peoples’ underlying opinions, and inform conversations aimed at bridging the gap between the general public and bodies of authority accordingly

Autonomic Nerve Activity and Blood Pressure in Ambulatory Dogs

Background The relationship between cardiac autonomic nerve activity and blood pressure (BP) changes in ambulatory dogs is unclear. Objective To test the hypotheses that simultaneous termination of stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA) predisposes to spontaneous orthostatic hypotension and that specific β2 adrenoceptor blockade prevents the hypotensive episodes. Methods We used a radiotransmitter to record SGNA, VNA and blood pressure (BP) in 8 ambulatory dogs. Video imaging was used to document postural changes. Results Out of these 8 dogs, 5 showed simultaneous sympathovagal discharges in which the minute by minute integrated SGNA correlated with integrated VNA in a linear pattern (“Group 1”). In these dogs abrupt termination of simultaneous SGNA-VNA at the time of postural changes (as documented by video imaging) was followed by abrupt (>20 mmHg over 4 beats) drops in BP. Dogs without simultaneous on/off firing (“Group 2”) did not have drastic drops in pressure. ICI 118,551 (ICI, a specific β2-blocker) infused at 3.1 µg/kg/hr for 7 days significantly increased BP from 126 (95% confidence interval, CI: 118 to 133) mmHg to 133 (95% CI 125 to141) mmHg (p=0.0001). The duration of hypotension (mean systolic BP < 100 mmHg) during baseline accounted for 7.1% of the recording. The percentage was reduced by ICI to 1.3% (p = 0.01). Conclusions Abrupt simultaneous termination of SGNA-VNA was observed at the time of orthostatic hypotension in ambulatory dogs. Selective β2 adrenoceptor blockade increased BP and reduced the duration of hypotension in this model