Comments: The Viability of the Trimester Approach

The Supreme Court established in Roe v. Wade a trimester test for determining the constitutionality of abortion regulations. In developing this test the Court relied upon contemporary medical knowledge. Because of recent advances in the medical field, it was unclear whether the trimester approach was in concert with these advances. This comment examines the development of the Roe test, discusses the present controversy concerning these medical advances, and analyzes three recent Supreme Court decisions dealing with the issue

Supporting Sustainability in a Distance Learning Curriculum

We have developed a suite of resources that help the audience focus on ways to connect to the sustainable development goals (United Nations, 2015). Key to our work is the idea that any actions should not be tokenistic but meaningful for colleagues and students who are engaging with our resources. We developed these resources into three stages of detail to bring the audience on a journey towards taking informed action. Stage 1 provides an opportunity to reflect on whether sustainability has been considered. Stage 2 outlines a range of resources grouped by theme alongside some suggested areas on where to begin to focus. Stage 3 infographics lead on from stage 2 and delve deeper into 4 areas of focus (1. Promoting competencies for sustainable development, 2. Engaging with existing resources, 3. Becoming more aware of what is happening within higher education, 4. Exploring opportunities to engage students in designing within the context of sustainable development) Supporting sustainability in a distance learning curriculum is not something that can be achieved without careful thought and consideration. It is important to acknowledge that we need to support our colleagues and stakeholders to engage in meaningful discussion and reflection. It is this that has brought us to where we are with the resources that we have created within this poster submission. Further scholarship will focus on reflecting on our next steps with regards to supporting colleagues and stakeholders to take non-tokenistic actions relating to sustainability in the curriculum

Scholarly insight Spring 2018: a Data wrangler perspective

In the movie classic Back to the Future a young Michael J. Fox is able to explore the past by a time machine developed by the slightly bizarre but exquisite Dr Brown. Unexpectedly by some small intervention the course of history was changed a bit along Fox’s adventures. In this fourth Scholarly Insight Report we have explored two innovative approaches to learn from OU data of the past, which hopefully in the future will make a large difference in how we support our students and design and implement our teaching and learning practices. In Chapter 1, we provide an in-depth analysis of 50 thousands comments expressed by students through the Student Experience on a Module (SEAM) questionnaire. By analysing over 2.5 million words using big data approaches, our Scholarly insights indicate that not all student voices are heard. Furthermore, our big data analysis indicate useful potential insights to explore how student voices change over time, and for which particular modules emergent themes might arise. In Chapter 2 we provide our second innovative approach of a proof-of-concept of qualification path way using graph approaches. By exploring existing data of one qualification (i.e., Psychology), we show that students make a range of pathway choices during their qualification, some of which are more successful than others. As highlighted in our previous Scholarly Insight Reports, getting data from a qualification perspective within the OU is a difficult and challenging process, and the proof-of-concept provided in Chapter 2 might provide a way forward to better understand and support the complex choices our students make. In Chapter 3, we provide a slightly more practically-oriented and perhaps down to earth approach focussing on the lessons-learned with Analytics4Action. Over the last four years nearly a hundred modules have worked with more active use of data and insights into module presentation to support their students. In Chapter 3 several good-practices are described by the LTI/TEL learning design team, as well as three innovative case-studies which we hope will inspire you to try something new as well. Working organically in various Faculty sub-group meetings and LTI Units and in a google doc with various key stakeholders in the Faculties, we hope that our Scholarly insights can help to inform our staff, but also spark some ideas how to further improve our module designs and qualification pathways. Of course we are keen to hear what other topics require Scholarly insight. We hope that you see some potential in the two innovative approaches, and perhaps you might want to try some new ideas in your module. While a time machine has not really been invented yet, with the increasing rich and fine-grained data about our students and our learning practices we are getting closer to understand what really drives our students

On-orbit servicing commercial opportunities with security implications

The On-Orbit Servicing (OOS) working group discussed legal and political implications of developing a commercial OOS industry. The group considered the benefits that OOS and Active Debris Removal (ADR) can offer the satellite industry, as well as potential disadvantages for international relations between space faring nations. To gain an accurate perspective of stakeholders involved in such a process, the OOS working group held a mock hearing for OOS licensing, with members of the working group assigned to represent stakeholders. Working group members presented their cases at a simulated domestic regulatory panel, constructed of members representing various government ministers, to fully explore stakeholder views. The mock hearings explored the challenges faced by OOS and ADR entrepreneurs as well as the benefit of regulation. The groups highlighted recommendations to ensure the practicality of OOS and determine how best to encourage licensing and regulation of such activities, as summarised below. 1. The United Nations (UN) should provide regulatory guidelines for OOS and ADR. 2. Government agencies should license OOS. The Federal Aviation Administration (FAA) has taken responsibility for licensing commercial space transportation in the United States and this should be extended to OOS/ADR missions to enable short-term advancement prior to further UN regulation. 3. Government should support OOS and ADR development to ensure continued demand. This includes leading by example on government satellites and potential launch levies to enable on-going ADR funding. 4. All stakeholders should prevent weaponisation of space through transparency of operations. 5. Nations should initiate international cooperation on ADR. OOS and ADR will ensure sustainable use of satellites, particularly in LEO and GEO, for the coming decades. It is through transparency, economic stimulation and close monitoring that such endeavours will be successful

Long Chain Polyunsaturated Fatty Acid Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention

A double-blind, randomized, controlled, parallel-group prospective trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid (DHA) supplementation on the cognitive performance of infants. A total of 122 term infants were fed one of four different formulas varying in their DHA composition (0.00%, 0.32%, 0.64% and 0.96% of total fatty acids as DHA) from birth to 12 months. The three DHA-supplemented formulas also contained 0.64% of total fatty acids as arachidonic acid (ARA, 20:4n-6). Infants were tested at 4, 6, and 9 months of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention. Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition; there was no dose-response for this effect. The distribution of time that infants spent in different phases of attention (a cognitive index derived from the convergence of behavioral and cardiac responses) varied as a function of dosage. Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula, while infants fed the highest dose were intermediate and did not differ from any other group

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era