Treaty Congestion in International Environmental Law: The Need for Greater International Coordination

The number of multilateral environmental agreements in the international community has proliferated greatly since the 1972 United Nations Conference on the Human Environment held in Stockholm, Sweden. When the conference was held in 1972, there were approximately three dozen multilateral environmental agreements in existence. In 1989, the United Nations\u27 Environmental Programme (UNEP) Register of Environmental Agreements listed a total of 139 treaties. Today, there are more than 900 international legal instruments, including treaties and binding or non-binding agreements that are either focused on [the] environment or contain one or more important provisions concerned with the environment. This growth and success in negotiating multilateral environmental agreements is likely to continue in the future

Risk Prediction of the Diabetes Missing Million: Identifying Individuals at High Risk of Diabetes and Related Complications

Early diagnosis and effective management of type 2 diabetes (T2D) are crucial in reducing the risk of developing life-changing complications such as heart failure, stroke, kidney disease, blindness and amputation, which are also associated with significant costs for healthcare providers. However, as T2D symptoms often develop slowly it is not uncommon for people to live with T2D for years without being aware of their condition—commonly known as the undiagnosed missing million. By the time a diagnosis is received, many individuals will have already developed serious complications. While the existence of undiagnosed diabetes has long been recognised, wide-reaching awareness among the general public, clinicians and policymakers is lacking, and there is uncertainty in how best to identify high-risk individuals. In this article we have used consensus expert opinion alongside the available evidence, to provide support for the diabetes healthcare community regarding risk prediction of the missing million. Its purpose is to provide awareness of the risk factors for identifying individuals at high, moderate and low risk of T2D and T2D-related complications. The awareness of risk predictors, particularly in primary care, is important, so that appropriate steps can be taken to reduce the clinical and economic burden of T2D and its complications

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051

Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins.

Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2. Once substantial antibody titres were generated, plasma was collected and samples pooled for each antigen. Non-specific antibodies were removed via affinity-purification to yield candidate products for testing in a hamster model of SARS-CoV-2 infection. Affinity-purified polyclonal antibodies to whole spike, S1 and S2 proteins were evaluated for in vitro for neutralising activity against SARS-CoV-2 Wuhan-like virus (Australia/VIC01/2020) and a recent variant of concern, B.1.1.529 BA.1 (Omicron), antibody-binding, complement fixation and phagocytosis assays were also performed. All antibody preparations demonstrated an effect against SARS-CoV-2 disease in the hamster model of challenge, with those raised against the S2 subunit providing the most promise. A rapid, cost-effective therapy for COVID-19 was developed which provides a source of highly active immunoglobulin specific to SARS-CoV-2 with multi-functional activity

Geobiology of a lower Cambrian carbonate platform, Pedroche Formation, Ossa Morena Zone, Spain

The Cambrian Pedroche Formation comprises a mixed siliciclastic-carbonate succession recording subtidal deposition on a marine platform. Carbonate carbon isotope chemostratigraphy confirms previous biostratigraphic assignment of the Pedroche Formation to the Atdabanian regional stage of Siberia, correlative to Cambrian Series 2. At the outcrop scale, thrombolitic facies comprise ~. 60% of carbonate-normalized stratigraphy and coated-grains another ~. 10%. Petrographic point counts reveal that skeletons contribute at most 20% to thrombolitic inter-reef and reef-flank lithologies; on average, archaeocyath clasts make up 68% of skeletal materials. In contrast, petrographic point counts show that skeletons comprise a negligible volume of biohermal and biostromal thrombolite, associated nodular carbonate facies, and ooid, oncoid and peloid grainstone facies. As such, archaeocyathan reefal bioconstructions represent a specific and limited locus of skeletal carbonate production and deposition. Consistent with data from coeval, globally dispersed lower Cambrian successions, our analysis of the Pedroche Formation supports the view that lower Cambrian carbonates have more in common with earlier, Neoproterozoic deposits than with younger carbonates dominated by skeletal production and accumulation. © 2013 Elsevier B.V.Jessica R. Creveling, David Fernández-Remolar, Marta Rodríguez-Martínez, Silvia Menéndez, Kristin D. Bergmann, Benjamin C. Gill, John Abelson, Ricardo Amils, Bethany L. Ehlmann, Diego C. García-Bellido, John P. Grotzinger, Christian Hallmann, Kathryn M. Stack, Andrew H. Knol

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination

Germany

A chapter in the book, East Central European Migrations During the Cold War, this chapter focuses on East German migration, especially after the Cold War.https://scholarlycommons.obu.edu/mono/1069/thumbnail.jp

Gender balance and impact of role models in secondary science education

Exposure to inspirational and relatable role models is crucial towards fostering engagement of learners with scientific disciplines. However, the representation of scientists in popular culture is still far from being adequately gender- and race-inclusive. This study evaluated the gender balance and impact of scientific role models using a two-pronged experimental approach. The gender balance was investigated in search engines, online databases, and school curricula. A survey was used to investigate English secondary students’ awareness of role models and intentions to pursue further scientific studies.Our findings revealed a widespread female underrepresentation amongst scientific role models in all the analysed online sources and in high school curricula provided by the three main English exam boards. The survey (n = 356) revealed that students were considerably more likely to identify famous male than female scientists. While awareness of female role models was significantly associated with students’ gender, this was not the case for male role models. A statistically significant correlation was also observed between the number of identified role models and intentions to pursue scientific studies in Key Stage 4 girls.This study reinforces the urgency of ensuring school curricula and online resources provide a more modern and inclusive representation of scientists

Learning from home during COVID-19: primary school parents’ perceptions of their school’s management of the home-learning situation

AbstractThe COVID-19 pandemic resulted in interruptions to social, economic, cultural, and educational life, with social distancing measures and well-being concerns leading to widespread restrictions to everyday activities. When COVID-19 first made an impact in 2020, many schools across Australia were closed entirely or provided limited access. Subsequently, many parents and caregivers were tasked with educating their children from home. Throughout this period, a key concern identified by various stakeholders was the potential impact of school closures on academic progression. This paper reports the results of a study that investigated Australian primary school parents’ experiences of home-learning with their children due to COVID-19 restrictions in 2020. To explore perceptions of how home-learning was managed by schools and the impact the experience had on children’s academic progress from the perspective of parents, survey data were collected (n = 171) and interviews were conducted (n = 29). The study was guided by Epstein’s Framework of Parental Involvement, with a particular focus on home-school partnerships. Findings indicated that, despite individual challenges, many parents were willing to engage in home-learning with their children, often beyond what was expected of them by the school. Overall, parents felt that the impact on academic progress was minimal, and that positive experiences were characterised by strong home-school connections. Through building on Epstein’s work to reconceptualise parental engagement with learning, rather than parental involvement with school, the study is important because it highlights assumptions made about parents’ pedagogical and content knowledge and their capacity to support school directed student learning. Importantly the findings demonstrate how home-school partnerships can be strengthened or put at risk under challenging conditions