A global scientific strategy to cure hepatitis B

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide

The evolution of the plastid chromosome in land plants: gene content, gene order, gene function

This review bridges functional and evolutionary aspects of plastid chromosome architecture in land plants and their putative ancestors. We provide an overview on the structure and composition of the plastid genome of land plants as well as the functions of its genes in an explicit phylogenetic and evolutionary context. We will discuss the architecture of land plant plastid chromosomes, including gene content and synteny across land plants. Moreover, we will explore the functions and roles of plastid encoded genes in metabolism and their evolutionary importance regarding gene retention and conservation. We suggest that the slow mode at which the plastome typically evolves is likely to be influenced by a combination of different molecular mechanisms. These include the organization of plastid genes in operons, the usually uniparental mode of plastid inheritance, the activity of highly effective repair mechanisms as well as the rarity of plastid fusion. Nevertheless, structurally rearranged plastomes can be found in several unrelated lineages (e.g. ferns, Pinaceae, multiple angiosperm families). Rearrangements and gene losses seem to correlate with an unusual mode of plastid transmission, abundance of repeats, or a heterotrophic lifestyle (parasites or myco-heterotrophs). While only a few functional gene gains and more frequent gene losses have been inferred for land plants, the plastid Ndh complex is one example of multiple independent gene losses and will be discussed in detail. Patterns of ndh-gene loss and functional analyses indicate that these losses are usually found in plant groups with a certain degree of heterotrophy, might rendering plastid encoded Ndh1 subunits dispensable

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

Challenges in power-imbalanced food supply: the UK case of small, specialist, and niche fresh produce relationships

This chapter seeks to identify and clarify successful business developments by specialist and niche businesses in the UK fresh produce market, related to the management of supplier–buyer relationships, and then relate the findings to the study of power-based supply chain relationships and networks. The focus is on the issues and challenges that face specialist suppliers when they work to improve their relationships with buyers. Serving a pivotal function in the link between primary producers and dominant retailers, channel intermediary organizations source from suppliers and then deal directly with supermarket retailers. This chapter will detail an enquiry, based on personal, in-depth interviews with the commercial directors of typical fresh produce intermediary businesses, into the best routes to market for small, specialist, and niche suppliers, as well as their best methods for managing channel and network relationships. Specifically: 1.Can satellite specialist suppliers manage channel power issues and business relationships despite their distance from the market? 2.What can specialist and niche suppliers offer, compared with large or generic suppliers?3.How might small specialist suppliers benefit from learning about the mechanisms of business relationships?The following discussion thus features implications for relevant academic theory, as well as practice pertaining to small business development, in relation to the management of supplier–buyer relationships.</p

Challenges in power-imbalanced food supply: the UK case of small, specialist, and niche fresh produce relationships

This chapter seeks to identify and clarify successful business developments by specialist and niche businesses in the UK fresh produce market, related to the management of supplier–buyer relationships, and then relate the findings to the study of power-based supply chain relationships and networks. The focus is on the issues and challenges that face specialist suppliers when they work to improve their relationships with buyers. Serving a pivotal function in the link between primary producers and dominant retailers, channel intermediary organizations source from suppliers and then deal directly with supermarket retailers. This chapter will detail an enquiry, based on personal, in-depth interviews with the commercial directors of typical fresh produce intermediary businesses, into the best routes to market for small, specialist, and niche suppliers, as well as their best methods for managing channel and network relationships. Specifically: 1.Can satellite specialist suppliers manage channel power issues and business relationships despite their distance from the market? 2.What can specialist and niche suppliers offer, compared with large or generic suppliers?3.How might small specialist suppliers benefit from learning about the mechanisms of business relationships?The following discussion thus features implications for relevant academic theory, as well as practice pertaining to small business development, in relation to the management of supplier–buyer relationships.</p

Transcriptomic and Histological Analysis of the Greentail Prawn (Metapenaeus bennettae) Following Light Crude Oil Exposure

Transcriptomic and Histological Analysis of the Greentail Prawn (Metapenaeus bennettae) Following Light Crude Oil Exposur