A Microfluidic Approach to Investigate the Contact Force Needed for Successful Contact-Mediated Nucleation

Emulsions with crystalline dispersed phase fractions are becoming increasingly important in the pharmaceutical, chemical, and life science industries. They can be produced by using two-stage melt emulsification processes. The completeness of the crystallization step is of particular importance as it influences the properties, quality, and shelf life of the products. Subcooled, liquid droplets in agitated vessels may contact an already crystallized particle, leading to so-called contact-mediated nucleation (CMN). Energetically, CMN is a more favorable mechanism than spontaneous nucleation. The CMN happens regularly because melt emulsions are stirred during production and storage. It is assumed that three main factors influence the efficiency of CNM, those being collision frequency, contact time, and contact force. Not all contacts lead to successful nucleation of the liquid droplet, therefore, we used microfluidic experiments with inline measurements of the differential pressure to investigate the minimum contact force needed for successful nucleation. Numerical simulations were performed to support the experimental data obtained. We were able to show that the minimum contact force needed for CMN increases with increasing surfactant concentration in the aqueous phase

Internship Experiences Contribute to Confident Career Decision Making for Doctoral Students in the Life Sciences.

The Graduate Student Internships for Career Exploration (GSICE) program at the University of California, San Francisco (UCSF), offers structured training and hands-on experience through internships for a broad range of PhD-level careers. The GSICE program model was successfully replicated at the University of California, Davis (UC Davis). Here, we present outcome data for a total of 217 PhD students participating in the UCSF and UC Davis programs from 2010 to 2015 and 2014 to 2015, respectively. The internship programs at the two sites demonstrated comparable participation, internship completion rates, and overall outcomes. Using survey, focus group, and individual interview data, we find that the programs provide students with career development skills, while increasing students' confidence in career exploration and decision making. Internships, in particular, were perceived by students to increase their ability to discern a career area of choice and to increase confidence in pursuing that career. We present data showing that program participation does not change median time to degree and may help some trainees avoid "default postdocs." Our findings suggest important strategies for institutions developing internship programs for PhD students, namely: including a structured training component, allowing postgraduation internships, and providing a central organization point for internship programs

Aspects Related to Fire Dynamics in Space Systems

No abstract availabl

Assessing ADHD symptoms in children and adults:Evaluating the role of objective measures

Background: Diagnostic guidelines recommend using a variety of methods to assess and diagnose ADHD. Applying subjective measures always incorporates risks such as informant biases or large differences between ratings obtained from diverse sources. Furthermore, it has been demonstrated that ratings and tests seem to assess somewhat different constructs. The use of objective measures might thus yield valuable information for diagnosing ADHD. This study aims at evaluating the role of objective measures when trying to distinguish between individuals with ADHD and controls. Our sample consisted of children (n = 60) and adults (n = 76) diagnosed with ADHD and matched controls who completed self- and observer ratings as well as objective tasks. Diagnosis was primarily based on clinical interviews. A popular pattern recognition approach, support vector machines, was used to predict the diagnosis. Results: We observed relatively high accuracy of 79% (adults) and 78% (children) applying solely objective measures. Predicting an ADHD diagnosis using both subjective and objective measures exceeded the accuracy of objective measures for both adults (89.5%) and children (86.7%), with the subjective variables proving to be the most relevant. Conclusions: We argue that objective measures are more robust against rater bias and errors inherent in subjective measures and may be more replicable. Considering the high accuracy of objective measures only, we found in our study, we think that they should be incorporated in diagnostic procedures for assessing ADHD

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill &amp; Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca