Banned Books Week

A panel discusses the importance of protecting books from being banned and challenged to protect our right to read

A review of inclusive business models and their application in aquaculture development

For aquaculture to continue along its current growth trajectory and contribute towards achieving the Sustainable Development Goals, value chains must become more inclusive. Smallholders and other local value chain actors are often constrained by circumstances and market failures in the global aquaculture industry. Integrating these actors into aquaculture value chains through inclusive business models (IBMs) is often touted as a solution to sustainable and ethical trade and business that can generate development outcomes. We reviewed 36 papers under seven business models commonly used in agriculture development to assess their application in aquaculture value chains in lower‐income countries. A global value chain (GVC) analysis is used to unpack the economic and social upgrading objectives of the different IBMs, as well as the types of relational coordination used between actors in the chain to achieve development outcomes. The extent to which these IBMs helped poor actors overcome certain barriers is evaluated with a focus on how they may ensure or be a risk to inclusiveness through the relations and upgrading opportunities evident in their make‐up. The analysis found that the majority of the models focused on economic upgrading over social upgrading. Providing opportunities for the latter is key to achieving the inclusive objectives of IBMs. Greater horizontal coordination between actors can create further opportunities for economic upgrading established under vertical coordination with other nodes upstream and downstream in a value chain. There is a need to further contextualize these models to aquaculture systems and develop clear indicators of inclusiveness

Governing for a Healthy Population: Towards an Understanding of How Decision-Making Will Determine Our Global Health in a Changing Climate

Enhancing the adaptive capacity of individuals, communities, institutions and nations is pivotal to protecting and improving human health and well-being in the face of systemic social inequity plus dangerous climate change. However, research on the determinants of adaptive capacity in relation to health, particularly concerning the role of governance, is in its infancy. This paper highlights the intersections between global health, climate change and governance. It presents an overview of these key concerns, their relation to each other, and the potential that a greater understanding of governance may present opportunities to strengthen policy and action responses to the health effects of climate change. Important parallels between addressing health inequities and sustainable development practices in the face of global environmental change are also highlighted. We propose that governance can be investigated through two key lenses within the earth system governance theoretical framework; agency and architecture. These two governance concepts can be evaluated using methods of social network research and policy analysis using case studies and is the subject of further research

Using a Markov Model and Real-World Evidence to Identify the Most Cost-Effective Cholesterol Treatment Escalation Threshold for the Secondary Prevention of Cardiovascular Disease.

BackgroundDespite the decreased risk of cardiovascular disease (CVD) with statins, there remains an unfulfilled clinical need to prevent CVD events and premature mortality through further cholesterol-modifying interventions. In people with established CVD taking a statin, lipid therapy escalation to reduce low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) levels may lower the risk of CVD hospital admissions and improve survival. However, the cost-effectiveness of different cholesterol treatment escalation thresholds is uncertain.ObjectiveThis study aimed to identify the most cost-effective cholesterol threshold for escalating lipid therapy in people with established CVD who are taking a statin, to support the 2023 update of the NICE guideline on CVD in England.MethodsA cohort Markov model with a yearly cycle length was developed to compare the lifetime costs and quality-adjusted life years (QALYs) of various LDL-C treatment escalation thresholds (0-4.0 mmol/L), using a combination of treatment effects from an original network meta-analysis of randomised controlled trials (RCTs), real-world data for estimating baseline cholesterol levels and CVD event rates from a published meta-analysis of statin RCTs. The model used the following CVD events: ischaemic stroke; transient ischaemic attack; peripheral artery disease; myocardial infarction; unstable angina; coronary revascularisation; and mortality. The model also used evidence-based estimates of resource use and costs, and published quality of life data. Baseline LDL-C levels and CVD hospital admission rates were estimated through a bespoke analysis of the English primary care data from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics Admitted Patient Care (HES) and Office for National Statistics (ONS) death registrations.ResultsData from 590,917 adult individuals (61.7% men) with CVD on a statin in primary care between 1 January 2013 and 28 February 2020 were included in the CPRD-HES-ONS analysis. The most cost-effective threshold for lipid therapy escalation was an LDL-C of 2.2 mmol/L (or equivalent non-HDL-C of 2.9 mmol/L) at NICE's lower cost per QALY of £20,000. An LDL-C of 2.0 mmol/L (or equivalent non-HDL-C of 2.6 mmol/L) was the most cost-effective treatment escalation threshold in a significant proportion (38%) of probabilistic simulations and produced more health. At this threshold, the model predicted that 42% of people with CVD would require combination therapy with ezetimibe while 19% would require an injectable drug such as inclisiran. At NICE's upper cost per QALY of £30,000, the most cost-effective LDL-C treatment escalation threshold was 1.7 mmol/L (or equivalent non-HDL-C of 2.2 mmol/L).ConclusionsThe results demonstrate the importance of establishing evidence of cost-effectiveness for cholesterol treatment escalation thresholds. The study's findings support the updated NICE guideline recommending a threshold of 2.0 mmol/L LDL-C (or equivalent non-HDL-C of 2.6 mmol/L) for secondary prevention of CVD

Federal Emergency Management Information System (FEMIS) Data Management Guide for FEMIS Version 1.4.6

The Federal Emergency Management Information System (FEMIS) is an emergency management planning and response tool that was developed by the Pacific Northwest National Laboratory (PNNL) under the direction of the U.S. Army Chemical Biological Defense Command. The FEMIS System Administration Guide provides information necessary for the system administrator to maintain the FEMIS system. The FEMIS system is designed for a single Chemical Stockpile Emergency Preparedness Program (CSEPP) site that has multiple Emergency Operations Centers (EOCs). Each EOC has personal computers (PCs) that emergency planners and operations personnel use to do their jobs. These PCs are corrected via a local area network (LAN) to servers that provide EOC-wide services. Each EOC is interconnected to other EOCs via a Wide Area Network (WAN). Thus, FEMIS is an integrated software product that resides on client/server computer architecture. The main body of FEMIS software, referred to as the FEMIS Application Software, resides on the PC client(s) and is directly accessible to emergency management personnel. The remainder of the FEMIS software, referred to as the FEMIS Support Software, resides on the UNIX server. The Support Software provides the communication data distribution and notification functionality necessary to operate FEMIS in a networked, client/server environment

A Multi-Center, Qualitative Assessment of Pediatrician and Maternal Perspectives on Rotavirus Vaccines and the Detection of Porcine circovirus

<p>Abstract</p> <p>Background</p> <p>In 2010, researchers using novel laboratory techniques found that US-licensed rotavirus vaccines contain DNA or DNA fragments from <it>Porcine circovirus </it>(PCV), a virus common among pigs but not believed to cause illness in humans. We sought to understand pediatricians' and mothers' perspectives on this finding.</p> <p>Methods</p> <p>We conducted three iterations of focus groups for pediatricians and non-vaccine hesitant mothers in Seattle, WA, Cincinnati, OH, and Rochester, NY. Focus groups explored perceptions of rotavirus disease, rotavirus vaccination, and attitudes about the detection of PCV material in rotavirus vaccines.</p> <p>Results</p> <p>Pediatricians understood firsthand the success of rotavirus vaccines in preventing severe acute gastroenteritis among infants and young children. They measured this benefit against the theoretical risk of DNA material from PCV in rotavirus vaccines, determining overall that the PCV finding was of no clinical significance. Particularly influential was the realization that the large, randomized clinical trials that found both vaccines to be highly effective and safe were conducted with DNA material from PCV already in the vaccines.</p> <p>Most mothers supported the ideal of full disclosure regarding vaccination risks and benefits. However, with a scientific topic of this complexity, simplified information regarding PCV material in rotavirus vaccines seemed frightening and suspicious, and detailed information was frequently overwhelming. Mothers often remarked that if they did not understand a medical or technical topic regarding their child's health, they relied on their pediatrician's guidance.</p> <p>Many mothers and pediatricians were also concerned that persons who abstain from pork consumption for religious or personal reasons may have unsubstantiated fears of the PCV finding.</p> <p>Conclusions</p> <p>Pediatricians considered the detection of DNA material from PCV in rotavirus vaccines a "non-issue" and reported little hesitation in continuing to recommend the vaccines. Mothers desired transparency, but ultimately trusted their pediatrician's recommendation. Both vaccines are currently approved for their intended use, and no risk of human PCV illness has been reported. Communicating this topic to pediatricians and mothers requires sensitivity to a broad range of technical understanding and personal concerns.</p

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1–3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia

International consensus on sleep problems in pediatric palliative care: paving the way

International audienc

Macrophage Therapy for Acute Liver Injury (MAIL): a study protocol for a phase 1 randomised, open-label, dose-escalation study to evaluate safety, tolerability and activity of allogeneic alternatively activated macrophages in patients with paracetamol-induced acute liver injury in the UK

Introduction: Acute liver failure (ALF) has no effective treatment other than liver transplantation and is commonly caused by paracetamol overdose. New treatments are needed to treat and prevent ALF. Alternatively-activated macrophages (AAMs) can promote resolution of liver necrosis and stimulate hepatocyte proliferation. Using AAMs in unscheduled care requires the use of an allogeneic product. A clinical trial is needed to determine the safety and tolerability of allogeneic AAMs. Methods and analysis: A single-centre, open-label, dose-escalation, phase 1 randomised trial to determine whether there is dose-limiting toxicity of AAMs in patients with paracetamol-induced acute liver injury. Randomisation will occur at higher doses. Between 17 and 30 patients will receive treatment, subject to dose-limiting toxicity and an adaptive trial design which aims to reduce the risk of allocation bias through blinding and randomisation. Ethics and dissemination: The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by North East—York Research Ethics Committee (reference 23/NE/0019), National Health Service Lothian Research and Development department, and the UK Medicines and Healthcare products Regulatory Agency. When the trial concludes, results will be shared by presentation and publication. Trial registration number: ISRCTN12637839