The Dividing Line

My best friend just called me a snob. It made me feel funny- like a child who has learned there is no Santa Claus..

H5N1 Virus Evolution in Europe—An Updated Overview

Since its emergence in South East Asia in 2003, Highly Pathogenic Avian Influenza (HPAI) A/H5N1 has reportedly caused outbreaks in poultry and/or wild birds in 62 countries, of which 24 were in Europe. Interestingly, out of the many genetic clades circulating in Asia, the westward spread of HPAI A/H5N1 to Central Asia, the Middle East, Europe and Africa was dominated by one single clade, namely clade 2.2. In this paper, we review and update through phylogenetic and gene migrational analysis the information concerning the evolution and the molecular epidemiology of HPAI A/H5N1 on the European continent

Mapping the regulatory landscape of AI in healthcare in Africa

Introduction: Artificial intelligence (AI)-enhanced technology has seen unprecedented expansion in the recent past. This growth brings with it huge opportunities for the positive transformation of the economy, business, healthcare, and society. However, a critical question is whether, and to what extent, regulatory measures and mechanisms have been implemented to safeguard its design, development, and deployment. This paper offers a scoping exercise that maps the regulatory landscape of AI in healthcare (including health research) in certain African countries.Methods: This research is conducted across 12 African countries: Botswana, Cameroon, The Gambia, Ghana, Kenya, Malawi, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. As limited specific AI legislation is found in these African countries, and because AI is informed by ancillary regulatory frameworks, we include data protection, digital health, consumer protection, and intellectual property in our research. A scoping review method was applied with a manual search of digital libraries with search terms customised for each repository consisting of core search terms for the various topics, including, among others, “law,” “regulation,” “artificial intelligence,” “data protection,” “intellectual property,” and “digital health”.Results and discussion: Analysis of the data demonstrated that while in the African countries under investigation there is no sui generis AI regulation, recent developments were found in areas that inform AI adoption, including in digital health, data protection, consumer protection, and intellectual property. Our findings highlight the fragmentation of the African AI regulatory landscape and illustrate the importance of continued AI regulatory development to ensure that Africa is well positioned for future AI adoption in health

Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy

Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α[superscript +] dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response. Due to decreased phagocytic ability post-maturation, DCs activated too early captured less antigen and could not effectively prime CD8[superscript +] T cells. Temporally programming DC activation to occur after tumoricidal activity enhanced tumor control by multiple distinct combination immunotherapies, highlighting dose schedule as an underappreciated factor that can profoundly affect the success of multi-component immunotherapies.National Cancer Institute (U.S.) (Grants NCI CA174795 and CA101830)Ludwig Center for Molecular Oncology at MIT (Graduate Fellowship)Thomas and Stacey Siebel Foundation (Scholarship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramHertz Foundation (Fellowship

Climate Change Engagement – Assessing the Impacts of the Climate Challenge Fund

The Scottish Government established the Climate Challenge Fund (CCF) in 2008 to help local communities in the transition to a low-carbon society. The fund supports community-led projects which lead to reductions in carbon emissions, and which are designed to leave a sustainable legacy of low-carbon behaviour. It works in areas such as energy efficiency, sustainable and active travel, reducing and recycling waste, and food growing. As of mid-2020, over 1,150 projects across all Scotland’s 32 local authorities had been awarded CCF grants, with total funding since 2008 exceeding £111 million. This report considers the evidence for the fund’s impact on the ground, the actions that were (and perhaps not) effective and how we can monitor success in the future. The research centres on in-depth case studies of five CCF projects which the team followed for 18 months. The report uses the case study evidence to understand and capture the processes of change supported by the CCF. From this, it draws out lessons on how to facilitate and monitor such impact going forward

The Iowa Homemaker vol.32, no.2

To a Bride, Salli Hearst, page 9 Happily Ever After, Donald C. Charles, page 10 The Bride Wore, Marilyn Bergeson and Patricia Keast, page 11 Here Comes the Bride, Marilyn Wright, page 12 Marriage and College - Yes, Gloria Sheehe, page 13 It’s All In the Family, Floramae Gates, page 14 With This Ring, Jean McGhie, page 15 Veiled In Loveliness, Evelyn Toulouse, page 16 Pots ‘n Pans, Maryann Meldrum, page 17 Proper Thing To Do, Marian Skinner, page 18 For Remembering, Marian Anderson, page 19 Weddings Without Worries, Nancy Voss, page 20 Showers, Joanne Ryals, page 21 Your Highest Hopes, Gayle Dunn, page 22 Bouquet for You, Maryann Meldrum, page 23 Your Trip to the Moon, Alane Baird, page 24 What’s New, Evelyn Toulouse and Dorothy Will, page 28 Information Please, Susan Brown and Mary Doherty, page 32 She Doesn’t Like Surprises and Neither Does He, Ruth Anderson, page 34 Breaking In the Groom, Alice Irvine, page 37 Trends, Joanne Ryals, page 3

Development and implementation of a national online application system for cross-jurisdictional linked data

The Population Health Research Network (PHRN) is an Australian national data linkage infrastructure that links a wide range of health and human services data in privacy-preserving ways. The data linkage infrastructure enables researchers to apply for access to routinely collected, linked, administrative data from the six states and two territories which make up the Commonwealth of Australia, as well as data collected by the Australian Government. The PHRN is a distributed network where data is collected and managed at the respective jurisdictional and/or cross-jurisdictional levels. As a result, access to linked data from multiple jurisdictions requires complex approval processes. This paper describes Australia's approach to enabling access to linked data from multiple jurisdictions. It covers the identification of, and agreement to, a minimum set of data items to be included in a unified national application form, the development and implementation of a national online application system and the harmonisation of business processes for cross-jurisdictional research projects. Utilisation of the online application system and the ongoing challenges of data linkage across jurisdictions are discussed. Changes to the data custodian and ethics committee approval criteria were out of scope for this project

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation-in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company's economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company's economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company's model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations

Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction

A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker

Survey Sequencing and Comparative Analysis of the Elephant Shark (Callorhinchus milii) Genome

Owing to their phylogenetic position, cartilaginous fishes (sharks, rays, skates, and chimaeras) provide a critical reference for our understanding of vertebrate genome evolution. The relatively small genome of the elephant shark, Callorhinchus milii, a chimaera, makes it an attractive model cartilaginous fish genome for whole-genome sequencing and comparative analysis. Here, the authors describe survey sequencing (1.4× coverage) and comparative analysis of the elephant shark genome, one of the first cartilaginous fish genomes to be sequenced to this depth. Repetitive sequences, represented mainly by a novel family of short interspersed element–like and long interspersed element–like sequences, account for about 28% of the elephant shark genome. Fragments of approximately 15,000 elephant shark genes reveal specific examples of genes that have been lost differentially during the evolution of tetrapod and teleost fish lineages. Interestingly, the degree of conserved synteny and conserved sequences between the human and elephant shark genomes are higher than that between human and teleost fish genomes. Elephant shark contains putative four Hox clusters indicating that, unlike teleost fish genomes, the elephant shark genome has not experienced an additional whole-genome duplication. These findings underscore the importance of the elephant shark as a critical reference vertebrate genome for comparative analysis of the human and other vertebrate genomes. This study also demonstrates that a survey-sequencing approach can be applied productively for comparative analysis of distantly related vertebrate genomes