31 research outputs found
Exploring the relationship between studentinstructor interaction on Twitter and student perception of teacher behaviors
With much attention being placed on the use of Twitter and other social media in the classroom, educators are grappling with the question, "Is Twitter a valid tool to increase classroom effectiveness?" Yet, many responses to this question come from anecdotal and case-study-based information. The present study offers a preliminary quantitative analysis of Twitter in the classroom. A survey-based experiment (n = 144) was conducted to measure student perceptions of teacher credibility, immediacy, and content relevance alongside instructor Twitter-use. Results indicate significant, positive correlations between student Twitter-use and positive perceptions of teacher behaviors. These results indicate that Twitter may serve as a valuable tool to supplement more traditional forms of course instruction
A New 24 micron Phase Curve for upsilon Andromedae b
We report the detection of 24 micron variations from the planet-hosting
upsilon Andromedae system consistent with the orbital periodicity of the
system's innermost planet, upsilon And b. We find a peak-to-valley phase curve
amplitude of 0.00130 times the mean system flux. Using a simple model with two
hemispheres of constant surface brightness and assuming a planetary radius of
1.3 Jupiter radii gives a planetary temperature contrast of >900 K and an
orbital inclination of >28 degrees. We further report the largest phase offset
yet observed for an extrasolar planet: the flux maximum occurs ~80 degrees
before phase 0.5. Such a large phase offset is difficult to reconcile with most
current atmospheric circulation models. We improve on earlier observations of
this system in several important ways: (1) observations of a flux calibrator
star demonstrate the MIPS detector is stable to 10^-4 on long timescales, (2)
we note that the background light varies systematically due to spacecraft
operations, precluding use of this background as a flux calibrator (stellar
flux measured above the background is not similarly affected), and (3) we
calibrate for flux variability correlated with motion of the star on the MIPS
detector. A reanalysis of our earlier observations of this system is consistent
with our new result.Comment: Submitted to ApJ. 15 pages, 6 figures, 4 table
R270C polymorphism leads to loss of function of the canine P2X7 receptor
The relative function of the P2X7 receptor, an ATP-gated ion channel, varies between humans due to polymorphisms in the P2RX7 gene. This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relative function of P2X7 on monocytes varied between individual dogs. The canine P2RX7 gene encoded four missense polymorphisms: F103L and P452S, found in heterozygous and homozygous dosage, and R270C and R365Q, found only in heterozygous dosage. Moreover, R270C and R365Q were associated with the cocker spaniel and Labrador retriever, respectively. F103L, R270C, and R365Q but not P452S corresponded to decreased P2X7 function in monocytes but did not explain the majority of differences in P2X7 function between dogs, indicating that other factors contribute to this variability. Heterologous expression of site-directed mutants of P2X7 in human embryonic kidney-293 cells indicated that the R270C mutant was nonfunctional, the F103L and R365Q mutants had partly reduced function, and the P452S mutant functioned normally. Taken together, these data highlight that a R270C polymorphism has major functional impact on canine P2X7
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
Future Experiences: Sustainable Development and the Global South
The Sustainable Development and the Global South project was jointly conceived by the Innovation School at Glasgow School of Art in partnership with the Sustainable Futures in Africa Network (SFA), and the University of Glasgow.
Graduating final year BDes Product Design students from the Innovation School were presented with a challenge-based project to produce a vision of the future based on current trends that relate to Sustainable Development work and the Global South. This project involved working closely with researchers, academics and professionals specialising in human geography, education, health, environment, engineering, cultural practice and community engagement who are part of the Sustainable Futures in Africa Network which includes a Scottish hub, led from the University of Glasgow. Included in the network was a representative from an NGO that builds schools in Malawi, an entrepreneur who runs an ethical clothing company that partners with producers in the Global South, a senior governance officer from the UK Government’s Department for International Development (DFID), a research network administrator, and international graduate students from Africa based at Scottish institutions. In addition to the SFA, external experts from design studio AndThen and GOODD design consultancy were engaged.
The objective of this project was to investigate, in both analytical and speculative ways, future forms and functions of Sustainable Development work in relation to the Global South in ten years from now, to develop future scenarios and design the artefacts, services and the experiences associated with these future visions. On completion of the project and learning experience it was intended that the students would be able to recognise and articulate the impact and sustainability of their design propositions, consider the life-cycle of their proposals and the values these might create for the intended users, communities and contexts.
The project was completed in January 2020, as the Covid-19 pandemic was just beginning its spread around the world. This unprecedented catastrophe reinforced the importance of supporting those most in need – the citizens of developing regions in the Global South. In April 2020, the heads of all the UN’s major agencies issued an open letter warning of the risks the virus posed to the world’s most vulnerable countries. It called on wealthier nations to increase funding and help to tackle issues such as the cessation of aid as a result of cancelled flights and disrupted supply routes. These and many other concerns highlighted during the crisis are among the topics explored in this project, which feels even more relevant and urgent than when it was initiated in the summer of 2019.
One of the most significant societal shifts currently taking place within the field of sustainable development work is its transformation from being understood as a process of growth or, at its most benign, poverty alleviation, to one of community empowerment and civic participation. The public’s role is developing beyond once-passive community members and recipients of aid, into stakeholders valued for their local knowledge, lived experiences, participation in development projects, and contribution towards policy-making and decision-making. This new dynamic is changing the traditional North-South relationship and holds the potential to challenge the geopolitical hegemony of International Development. The impetus for this shift is a decolonial, collaborative approach to development, research and practice; increased local empowerment, and sustainable solutions to problems that are co-created in context with those affected by and affecting the issue in question.
This project asked students to consider what happens in this global landscape ten years from now where Sustainable Development has evolved to the extent that new forms of work and communities of practice transform how people engage, learn and interact with each other, with stakeholders and with the global community around them. The brief gave students the opportunity to explore the underlying complexities regarding sustainable futures, the post-colonial dynamic between ‘norths’ and ‘souths’, post-capitalism and human agency, to envision a future world context, develop it as an experiential exhibit, and produce the designed products, services and experiences for the people who might live and work within it.
The project was divided into two sections: The first was a collaborative stage where groups of students were assigned a specific domain to collectively research one aspect of the project challenge, these domains included; Health, Energy, Mobility, Economies, Education, Societal Structures and Environment. Each of these domains were examined through the lenses of Social, Technological, Economic, Ethical, Educational, Values, Political, Legal and Ecological (STEEEVPLE) and were tailored in use, as appropriate per domain. The groups focused on researching and exploring their specific domain and gathering as much information and understanding while working with the external experts to further their knowledge. This group stage culminated in a series of Future World exhibits which tangibly manifest the cohort’s collective knowledge and collaborative understanding of what the future could look like in 10 years from now, after exploring the possible consequences of current actions.
The second stage saw students explore their individual response to the Future World that had been created in the first stage. Each student developed their own response to the research by iteratively creating a design outcome that was appropriate to the subject matter. This culminated in each student producing a designed product, service or system and a visual communication of the future experience which they had created.
A visual summary of the journey and stages (Project Journey Map) is included within the repository and outlines the collaborative process of designing and the innovative nature of the project’s pedagogical model.
The project aims to reveal and address the emerging possibilities collaboratively created by Sustainable Development professionals and designers interacting and learning from each other, to present preferable futures which reveal socio-ecological innovations in development work with the Global South in the near future.
The deposited materials are arranged as follows:
Readme files - two readme files relate to stage one and stage two of the project as outlined above.
Project Journey Map - gives a visual overview of the pedagogical structure and timeline of the project.
Data folders - the data folders for stage one of the project are named by the domains through which each group explored possible futures. The data folders for stage two of the project are named for the individual students who conducted the work
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
ASSOCIATIONS OF TRIMETHYLAMINE N-OXIDE AND ITS PRECURSORS WITH GESTATIONAL DIABETES AND PRE-ECLAMPSIA AMONG WOMEN DELIVERING AT AN URBAN SAFETY NET HOSPITAL
Introduction: Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in non-pregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking.
Methods: We used data from the Boston Birth Cohort between 1998 and 2013. We examined associations of TMAO, choline, betaine, and carnitine measured in both cord blood and maternal blood with gestational diabetes mellitus (GDM) and pre-eclampsia (PE). We used logistic regression to estimate odds ratios for each outcome according to tertiles and a standard deviation (SD) increment of TMAO, choline, betaine, and carnitine. Final models were adjusted for potential confounders.
Results: Among our analytic sample of 1496 women, 115 developed GDM and 158 PE. Inter-metabolite correlations of TMAO and its precursors were stronger within cord blood (r=0.38-0.87) than within maternal blood (r=0.08-0.62). Among the maternal blood metabolites analyzed, TMAO was associated with higher odds of GDM (3rd vs. 1st tertile OR=1.75; 95% CI 1.04, 2.94), while TMAO precursor metabolites were not associated with GDM. Concentrations of TMAO and choline in maternal blood were not associated with PE, while maternal blood carnitine was associated with higher odds of PE (OR=1.92; 95% CI 1.21, 3.04) and betaine was associated with lower odds of PE (OR=0.37; 95% CI 0.23, 0.59). In cord blood, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine measured in cord blood were associated with higher odds of PE (OR=3.11; 95% CI 1.62, 5.96; OR=2.65; 95% CI 1.42, 4.93); OR=2.56; 95% CI 1.39, 4.69; respectively). In addition, cord choline was associated with lower odds of GDM (OR=0.52; 95% CI 0.27, 0.99), while other cord metabolites were not associated with GDM.
Conclusion: Our study adds to the evidence that TMAO and its precursors play an etiologic role in development of GDM and PE
ASSOCIATIONS OF TRIMETHYLAMINE N-OXIDE AND ITS PRECURSORS WITH GESTATIONAL DIABETES AND PRE-ECLAMPSIA AMONG WOMEN DELIVERING AT AN URBAN SAFETY NET HOSPITAL
Introduction: Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in non-pregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking.
Methods: We used data from the Boston Birth Cohort between 1998 and 2013. We examined associations of TMAO, choline, betaine, and carnitine measured in both cord blood and maternal blood with gestational diabetes mellitus (GDM) and pre-eclampsia (PE). We used logistic regression to estimate odds ratios for each outcome according to tertiles and a standard deviation (SD) increment of TMAO, choline, betaine, and carnitine. Final models were adjusted for potential confounders.
Results: Among our analytic sample of 1496 women, 115 developed GDM and 158 PE. Inter-metabolite correlations of TMAO and its precursors were stronger within cord blood (r=0.38-0.87) than within maternal blood (r=0.08-0.62). Among the maternal blood metabolites analyzed, TMAO was associated with higher odds of GDM (3rd vs. 1st tertile OR=1.75; 95% CI 1.04, 2.94), while TMAO precursor metabolites were not associated with GDM. Concentrations of TMAO and choline in maternal blood were not associated with PE, while maternal blood carnitine was associated with higher odds of PE (OR=1.92; 95% CI 1.21, 3.04) and betaine was associated with lower odds of PE (OR=0.37; 95% CI 0.23, 0.59). In cord blood, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine measured in cord blood were associated with higher odds of PE (OR=3.11; 95% CI 1.62, 5.96; OR=2.65; 95% CI 1.42, 4.93); OR=2.56; 95% CI 1.39, 4.69; respectively). In addition, cord choline was associated with lower odds of GDM (OR=0.52; 95% CI 0.27, 0.99), while other cord metabolites were not associated with GDM.
Conclusion: Our study adds to the evidence that TMAO and its precursors play an etiologic role in development of GDM and PE
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Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.
BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity
Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program
Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). Results: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. Discussion: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions