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Currently, the entire globe is affected by the COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2(SCV2). The ability to detect, monitor and assess the spread of the virus is imperative to controlling the effects of the pandemic. In order to meet the need for global testing, several methods have been developed. As a complement to individual testing, wastewater-based epidemiology represents a low-cost way to estimate the prevalence of the virus in a community. This information can be used to influence public policy regarding viral mitigation measures. This thesis documents our efforts at implementing wastewater testing in Santa Cruz County over the past 18 months. We sampled from the Watsonville Wastewater Treatment Plant on a weekly basis and quantified the presence of SCV2 using reverse transcriptase digital PCR normalized to Pepper Mild Mottle Virus (PMMV). Our data showed a large discrepancy between reported case counts and SCV2 in wastewater. This data also revealed seasonal variation in PMMV, potentially hindering it as a reliable normalizer. In addition to our sewage work, we performed masked-based sampling for Pacific Elementary School and documented a probable positive. This work demonstrates the potential of sewage sampling for SARS-CoV-2 and some of the current unmet challenges in both sewage sampling and pandemic response as a whole.

World Bank Group President, David Malpass spoke about how the past four weeks the World Bank has begun to implement twelve billion-dollar package that would enable vaccination systems for countries that otherwise wouldn't have access, and that was the goal. He explained the assessment of the countries and their ability to deliver vaccines. He mentioned one of the big challenges for the world is how to create systems where people that are poor can build assets. One of the most valuable assets that people have is education, and the second is an actual job. The World Bank wants to amplify social safety nets around the world to get cash or other kinds of support to the poor. That has been a challenge. The debt crisis has been a challenge because you can identify countries where the World Bank would put in resources but all of that would go to creditors, and none of it to the people. Once the grace period runs out for Bank loans, in reality it is a loan that is not going to be paid, and some of the banking systems will come under pressure from domestic debt. One of the challenges that the G20 faces is how to get broad debt relief to countries that were over-indebted. He plugged for trade facilitation. The most important thing for economic development is to quickly get things across borders.

ispartof: The European Academy of Occupational Health Psychology (EAOHP) location:online date:2 Sep - 4 Sep 2020 status: published

ispartof: Algemene Vergadering OKRA-Sport location:Webinar status: published

One in five undergraduates (22%) and graduate and professional students (19%) enrolled at large public research universities experienced food insecurity, according to the Student Experience in the Research University (SERU) Consortium survey of 31,687 undergraduate students at nine universities and 16,453 graduate and professional students from ten universities during the early months of the COVID-19 pandemic. Results from the survey suggest that undergraduate, graduate, and professional students from underrepresented and marginalized backgrounds experienced significantly higher rates of food insecurity compared to their peers.Specifically Black, Hispanic and Latinx, American Indian or Alaskan Native, and international students; low-income, poor, or working-class students; students who are caregivers to adults during the pandemic; first-generation students; and students who are transgender, nonbinary, bisexual, pansexual, or queer all experienced significantly higher rates of food insecurity during the pandemic compared to their peers.

David Malpass, President of the World Bank Group, summarized the challenging environment now facing the World Bank Group, as the unprecedented COVID-19 pandemic affects the world. He is expecting a major global recession to complicate the devastating health crisis. The extreme poor in IDA countries will be severely affected. He reviewed the measures taken by the World Bank Group in response to the emergency. The program has three pillars: protecting the poorest and most vulnerable households; supporting businesses and saving jobs; implementing emergency health operations in developing countries to strengthen economic resilience. To this end, USD 160 billion in financing over the next 15 months are available. He summarized the debt relief initiative championed at the G20 meeting. He recapped the activities during the Spring meetings and recent high-level appointments.

Objective/Purpose: More than 16 months after its first detection, the COVID-19 pandemic has resulted in over 159 million cases and 3.3 million deaths worldwide.1 The purpose of this study is to describe the potential associations between being a healthcare worker and two outcomes of COVID-19 infection: hospitalization and death. Methods: We conducted detailed descriptive analyses of all incident COVID-19 cases ascertained as part of the passive surveillance system instituted by the CDC from the 50 United States, Puerto Rico, and the US Virgin Islands between 2/1/2020 and 2/28/2021. We modeled the associations between healthcare worker status and two clinical outcomes of COVID-19 infection by individual U.S. state using multivariable multinomial logistic regressions, adjusting for sex, race/ethnicity, age group, and presence of pre-existing conditions. Results: After adjustment, we observed that healthcare workers in Colorado, Louisiana, Massachusetts, and Ohio had lower odds of both hospitalization and death compared to those who were not healthcare workers. In addition, we noticed a pattern of higher odds of both hospitalization and death in people with unknown healthcare worker status compared to non-healthcare workers in all 12 states/territories assessed. Those with unknown healthcare worker status had the highest odds of hospitalization in the state of Utah (odds ratio, OR 11.73; 95% CI 9.51-14.46) and death in the state of Colorado (OR 13.99; 95% CI 3.12-62.68). The hospitalization ORs for healthcare workers and those with unknown healthcare worker status ranged from 0.27 to 11.73, while the death ORs ranged from 0.19 to 13.99. Conclusions: The study results demonstrated that being a healthcare worker in the US was associated with less hospitalization and death from COVID-19 infection while having unknown healthcare worker status is associated with greater hospitalization and death. This study underscores the necessity for additional analyses of COVID-19 infection outcomes among both non-healthcare and healthcare workers, as well as the importance of complete data collection for disease surveillance systems.

Countries in Africa should strive to maintain trade flows during the crisis to secure access to medical goods and services, and food and other essential items such as farm inputs. This requires keeping borders open to the largest extent possible and avoiding measures such as export bans or taxes. Countries should take action to reduce taxes and duties on trade, to streamline trade procedures and to support transport and logistics services in maintaining cross-border and international value chains. By joining together, countries in Africa can implement coordinated trade measures that result in better responses to the crisis. Joint actions include bilateral cooperation on border management, joint information campaigns, coordinated purchasing of medical equipment, partnering on repurposing production to produce medical goods, and management of health specialists to deal with emerging hotspots on the continent. Development partners should support coordinated actions by regional institutions through analysis, technical assistance and perhaps operational projects. Identifying the appropriate level (sub-national, national, regional, continental) for interventions and the most effective institutions, in terms of relevance and capacity, to manage coordinated actions will be essential.

Covalent drugs incorporate a mildly electrophilic functional group that reacts with protein targets to confer additional affinity beyond the non-covalent interactions involved in drug binding. In the past, concerns about these reactive molecules’ interference with biological assays and lack of selectivity often discouraged further investigation. However, the emergence of intentionally designed covalent drugs against major disease targets over the last ten years showcases the strengths of this field. The first part of this thesis will review the historical and modern milestones in covalent drug discovery with emphasis on chemoproteomics techniques that enable success, and the remaining chapters will address my contributions to the field through the development of tool covalent compounds as novel inhibitors and new induced proximity platforms.Chemoproteomics-enabled covalent ligand screening platforms can be used to identify novel ligands against undruggable protein targets like MYC. MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. I performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt the binding of MYC to its DNA consensus sequence in vitro and also impair MYC transcriptional activity in situ in cells. I identified a covalent ligand EN4 that targets cysteine 171 (C171) of MYC within a predicted intrinsically disordered region of the protein. I show that EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. I also show initial structure-activity relationships of EN4 and identify compounds that show improved potency. Overall, I identified a novel ligandable site within an intrinsically disordered region of MYC that leads to inhibition of MYC transcriptional activity. In addition to facilitating the discovery of covalent small-molecule allosteric modulators of disease relevant proteins and pathways, chemoproteomics-enabled covalent drug discovery also proves useful in identifying inhibitors of critical disease proteins that contain catalytic cysteines. Among the various genes and proteins encoded by all coronaviruses, one particularly “druggable” or relatively easy-to-drug target is the coronavirus Main Protease (3CLpro or Mpro), a cysteine-protease that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro’s catalytic cysteine with a small-molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit across coronaviruses. As part of a collaborative effort, I utilized activity-based protein profiling (ABPP)- chemoproteomic approaches to discover and further optimize cysteine-reactive pyrazoline-based covalent inhibitors for the SARS-CoV-2 Mpro. Structure-guided medicinal chemistry and modular synthesis of di- and tri-substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine-reactive warheads enabled the expedient exploration of structure-activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS-CoV-2, but across many previous coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan-coronavirus inhibitors. Finally, chemoproteomics-enabled drug discovery platforms facilitate the expansion of targeted protein degradation and related fields. Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). We designed deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small molecules consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 covalent recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS.

World Bank Group President David Malpass spoke about how in its first year, the Coronavirus (COVID-19) pandemic is pushing one hundred fifty million people into extreme poverty, ending two decades of steady progress on poverty reduction. Coronavirus (COVID-19) has altered every aspect of commercial activity and trade, shrinking gross domestic products (GDP), fueling a debt crisis and triggering severe food crises. He cautioned about the long-standing problems in the global food system, and how World Food Programme (WFP) and Food and Agriculture Organization (FAO) has estimated that the number of people facing acute food insecurity will double to two hundred sixty-five million people in 2020. He spoke about working along with IMF on effective approaches for debt reduction and debt resolution to address low income countries’ unsustainable debt burdens. He highlighted on establishing a fast-track Coronavirus (COVID) response that has delivered emergency support to one hundred twelve countries so far. He explained that in response to the global food security crisis, the World Bank Group has significantly stepped up investments to strengthen food security in client countries.