Research ethics and artificial intelligence for global health: perspectives from the global forum on bioethics in research.

BACKGROUND: The ethical governance of Artificial Intelligence (AI) in health care and public health continues to be an urgent issue for attention in policy, research, and practice. In this paper we report on central themes related to challenges and strategies for promoting ethics in research involving AI in global health, arising from the Global Forum on Bioethics in Research (GFBR), held in Cape Town, South Africa in November 2022. METHODS: The GFBR is an annual meeting organized by the World Health Organization and supported by the Wellcome Trust, the US National Institutes of Health, the UK Medical Research Council (MRC) and the South African MRC. The forum aims to bring together ethicists, researchers, policymakers, research ethics committee members and other actors to engage with challenges and opportunities specifically related to research ethics. In 2022 the focus of the GFBR was "Ethics of AI in Global Health Research". The forum consisted of 6 case study presentations, 16 governance presentations, and a series of small group and large group discussions. A total of 87 participants attended the forum from 31 countries around the world, representing disciplines of bioethics, AI, health policy, health professional practice, research funding, and bioinformatics. In this paper, we highlight central insights arising from GFBR 2022. RESULTS: We describe the significance of four thematic insights arising from the forum: (1) Appropriateness of building AI, (2) Transferability of AI systems, (3) Accountability for AI decision-making and outcomes, and (4) Individual consent. We then describe eight recommendations for governance leaders to enhance the ethical governance of AI in global health research, addressing issues such as AI impact assessments, environmental values, and fair partnerships. CONCLUSIONS: The 2022 Global Forum on Bioethics in Research illustrated several innovations in ethical governance of AI for global health research, as well as several areas in need of urgent attention internationally. This summary is intended to inform international and domestic efforts to strengthen research ethics and support the evolution of governance leadership to meet the demands of AI in global health research.

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, to our knowledge none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage [Formula: see text], a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We use a high-throughput gene editing-phenotyping technology to measure [Formula: see text]'s fitness landscape in the presence of different evolved-[Formula: see text] competitors and find that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulate [Formula: see text]'s evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. [Formula: see text] heterogeneity only evolves in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage λ, a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We used a high-throughput gene editing-phenotyping technology to measure λ's fitness landscape in the presence of different evolved-λ competitors and found that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulated λ's evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. λ heterogeneity only evolved in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

The importance of getting the ethics right in a pandemic treaty.

The COVID-19 pandemic revealed numerous weaknesses in pandemic preparedness and response, including underfunding, inadequate surveillance, and inequitable distribution of countermeasures. To overcome these weaknesses for future pandemics, WHO released a zero draft of a pandemic treaty in February, 2023, and subsequently a revised bureau's text in May, 2023. COVID-19 made clear that pandemic prevention, preparedness, and response reflect choices and value judgements. These decisions are therefore not a purely scientific or technical exercise, but are fundamentally grounded in ethics. The latest treaty draft reflects these ethical considerations by including a section entitled Guiding Principles and Approaches. Most of these principles are ethical-they establish core values that undergird the treaty. Unfortunately, the treaty draft's set of principles are numerous, overlapping, and show inadequate coherence and consistency. We propose two improvements to this section of the draft pandemic treaty. First, key guiding ethical principles should be clearer and more precise than they currently are. Second, the link between ethical principles and policy implementation should be clearly established and define boundaries on acceptable interpretation, ensuring that signatories abide by these principles.

Equitable global allocation of monkeypox vaccines.

With the world grappling with continued spread of monkeypox internationally, vaccines play a crucial role in mitigating the harms from infection and preventing spread. However, countries with the greatest need - particularly historically endemic countries with the highest monkeypox case-fatality rates - are not able to acquire scarce vaccines. This is unjust, and requires rectification through equitable allocation of vaccines globally. We propose applying the Fair Priority Model for such allocation, which emphasizes three key principles: 1) preventing harm; 2) prioritizing the disadvantaged; and 3) treating people with equal moral concern. Post-exposure prophylaxis (PEPV) has the most potential to mitigate harm, and so ensuring countries have sufficient supply for PEPV should be the first priority. And historically endemic countries, which face disadvantages that compound potential harms from monkeypox, should be the first recipients of such vaccines. Once sufficient supply is allocated for countries to apply PEPV, global allocation could move on to pre-exposure prophylaxis (PrEP), again prioritizing historically endemic countries first before distribution to the rest of the global community, based on projected number of cases and vulnerability to harm.

Acute uterine inversion following an induced abortion.

Acute uterine inversion is a rare and potentially life-threatening obstetric emergency. Its occurrence as a result of a mid-trimester abortion is an even rarer consequence. We report a case of a 32-year-old woman who presented with complete acute uterine inversion and hemorrhagic shock following an incomplete medical abortion at 14 weeks of gestation. Our attempts at non-operative reversal of the inversion failed. Therefore, we resorted to the manual replacement of the uterus via laparotomy without using surgical instruments or an incision in the cervical ring. The laparotomic manual replacement served as a successful alternative with minimal immediate or long-term morbidity that may have resulted from trauma and scarring of the uterus.

Towards a new model of global health justice: the case of COVID-19 vaccines.

This paper questions an exclusively state-centred framing of global health justice and proposes a multilateral alternative. Using the distribution of COVID-19 vaccines to illustrate, we bring to light a broad range of global actors up and down the chain of vaccine development who contribute to global vaccine inequities. Section 1 (Background) presents an overview of moments in which diverse global actors, each with their own priorities and aims, shaped subsequent vaccine distribution. Section 2 (Collective action failures) characterises collective action failures at each phase of vaccine development that contributed to global vaccine disparities. It identifies as critical the task of establishing upstream strategies to coordinate collective action at multiple stages across a range of actors. Section 3 (A Multilateral model of global health governance) takes up this task, identifying a convergence of interests among a range of stakeholders and proposing ways to realise them. Appealing to a responsibility to protect (R2P), a doctrine developed in response to human rights atrocities during the 1990s, we show how to operationalise R2P through a principle of subsidiarity and present ethical arguments in support of this approach.

Global sharing of COVID-19 therapies during a "New Normal".

This paper argues for global sharing of COVID-19 treatments during the COVID-19 pandemic and beyond based on principles of global solidarity. It starts by distinguishing two types of COVID-19 treatments and models sharing strategies for each in small-group scenarios, contrasting groups that are solidaristic with those composed of self-interest maximizers to show the appeal of solidaristic reasoning. It then extends the analysis, arguing that a similar logic should apply within and between nations. To further elaborate global solidarity, the paper distinguishes morally voluntary, sliding-scale, and mandatory versions. It argues for an all-hands-on-deck approach and gives examples to illustrate. The paper concludes that during the COVID-19 crisis, global solidarity is a core value, and global sharing of COVID-19 treatments should be considered a duty of justice, not of charity.

Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds.

Chronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could three dimensional-map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic (PA) ultrasound (US) is a non-invasive, hybrid imaging modality that can solve these major limitations. PA relies on the contrast generated by haemoglobin in blood which allows it to map local angiogenesis, tissue perfusion and oxygen saturation-all critical parameters for wound healing. This work evaluates the use of PA-US to monitor angiogenesis and stratify patients responding versus not-responding to therapy. We imaged 19 patients with 22 wounds once a week for at least 3 weeks. Our findings suggest that PA imaging directly visualises angiogenesis. Patients responding to therapy showed clear signs of angiogenesis and an increased rate of PA increase (p = 0.002). These responders had a significant and negative correlation between PA intensity and wound size. Hypertension was correlated to impaired angiogenesis in non-responsive patients. The rate of PA increase and hence the rate of angiogenesis was able to predict healing times within 30 days from the start of monitoring (power = 88%, alpha = 0.05). This early response detection system could help inform management and treatment strategies while improving outcomes and reducing costs.

Photoacoustic imaging to monitor outcomes during hyperbaric oxygen therapy: validation in a small cohort and case study in a bilateral chronic ischemic wound.

Hyperbaric oxygen therapy (HBO2) is a common therapeutic modality that drives oxygen into hypoxic tissue to promote healing. Here, ten patients undergoing HBO2 underwent PA oximetry of the left radial artery and forearm pre- and post-HBO2; this cohort validated the use of PA imaging in HBO2. There was a significant increase in radial artery oxygenation after HBO2 (p = 0.002) in the validation cohort. We also include a case study: a non-diabetic male in his 50s (HB 010) presenting with bilateral ischemic and gangrenous wounds. HB 010 showed higher perfusion and oxygen saturation on the right foot than the left after HBO2 which correlated with independent surgical observations. Imaging assisted with limb salvage treatment. Hence, this work shows that PA imaging can measure changes in arterial oxygen saturation due to HBO2; it can also produce 3D maps of tissue oxygenation and evaluate response to therapy during HBO2.

What's yours is ours: waiving intellectual property protections for COVID-19 vaccines.

This paper gives an ethical argument for temporarily waiving intellectual property (IP) protections for COVID-19 vaccines. It examines two proposals under discussion at the World Trade Organization (WTO): the India/South Africa proposal and the WTO Director General proposal. Section I explains the background leading up to the WTO debate. Section II rebuts ethical arguments for retaining current IP protections, which appeal to benefiting society by spurring innovation and protecting rightful ownership. It sets forth positive ethical arguments for a temporary waiver that appeal to standing in solidarity and holding companies accountable. After examining built-in exceptions to existing agreements and finding them inadequate, the paper replies to objections to a temporary waiver and concludes, in section III, that the ethical argument for temporarily waiving IP protection for COVID-19 vaccines is strong.

Point-of-Care Ultrasound as a Tool to Assess Wound Size and Tissue Regeneration after Skin Grafting.

Chronic wounds can be difficult to heal and are often accompanied by pain and discomfort. Multiple skin substitutes or cellularized/tissue-based skin products have been used in an attempt to facilitate closure of complex wounds. Allografts from cadaveric sources have been a viable option in achieving such closure. However, early assessment of graft incorporation has been difficult clinically, often with delayed evidence of failure. Visual cues to assess graft integrity have been limited and remain largely superficial at the skin surface. Furthermore, currently used optical imaging techniques can penetrate only a few millimeters deep into tissue. Ultrasound (US) imaging offers a potential solution to address this limitation. This work evaluates the use of US to monitor wound healing and allograft integration. We used a commercially available dual-mode (US and photoacoustic) scanner operating only in US mode. We compared the reported wound size from the clinic with the size measured using US in 45 patients. Two patients from this cohort received an allogenic skin graft and underwent multiple US scans over a 110-d period. All data were processed by two independent analysts; one of them was blinded to the study. We measured change in US intensity and wound contraction as a function of time. Our results revealed a strong correlation (R2 = 0.81, p < 0.0001) between clinically and US-measured wound sizes. Wound contraction >91% was seen in both patients after skin grafting. An inverse relationship between wound size and US intensity (R2 = 0.77, p < 0 .0001) indicated that the echogenicity of the wound bed increases as healthy cells infiltrate the allograft matrix, regenerating and leading to healthy tissue and re-epithelization. This work indicates that US can be used to measure wound size and visualize tissue regeneration during the healing process.

Medical oncology care amidst the COVID-19 pandemic at the National University Hospital in the Philippines.

COVID-19 has abruptly and radically changed the landscape of cancer care delivery throughout the world, including the Philippines. The Philippine General Hospital is the academic hospital of the University of the Philippines. Its cancer centre is a primary referral centre that takes care of Filipinos-many resource-constrained-that are burdened by malignancy. As the global pandemic challenges healthcare delivery, centres are forced to rethink how to care for their patients. This paper discusses how a national, academic, referral cancer institute in a low-middle income country is trying to meet the challenges of COVID-19.

Articulating the sources for an African normative framework of healthcare: Ghana as a case study.

Bioethics is gradually becoming an important part of the drive to increase quality healthcare delivery in sub-Saharan African countries. Yet many healthcare service-users in Africa are familiar with incidences of questionable health policies and poor healthcare delivery, leading to severe consequences for patients. We argue that the overarching rights-based ethical administrative framework recently employed by healthcare authorities contributes to the poor uptake and enforcement of current normative tools. Taking Ghana as a case study, we focus on the cultural ethical context and we tease out the concepts of the good and the ethical among the Akan and Bulsa ethnic groups. We point out three tenets towards building a normative framework that can resonate with service-users and practitioners: ontological communitarianism; empathic humanism; and virtuous character. Finally, we indicate how these core tenets can be dovetailed into building an effective normative framework and into the training of healthcare providers.

Topical Selenium Sulfide for the Treatment of Hyperkeratosis.

Hyperkeratosis presents as thickened skin. It can be congenital or acquired. Typically, it affects the palms and soles; the distribution of epidermal involvement is either diffuse, focal, or punctate. Microscopically, the pathologic signature of hyperkeratosis is marked orthokeratosis of the stratum corneum. Topical treatments provide the mainstay of therapy for hyperkeratosis. These include keratolytics (such as urea, salicylic acid, and lactic acid) and retinoids; physical debridement, topical corticosteroids, and phototherapy (using topical psoralen and ultraviolet A phototherapy) are other local therapeutic modalities. Selenium is a non-metallic essential element; its water-insoluble salt, selenium sulfide, is an active ingredient that is used (in either a foam, lotion, or shampoo) to treat not only seborrheic dermatitis but also tinea versicolor. Three individuals with hyperkeratosis involving their palms and/or soles are described; the hyperkeratosis was successful treated with topical selenium sulfide in either a 2.5% lotion/shampoo or a 2.75% foam. The response to topical selenium sulfide was not only rapid but also complete and sustained; none of the patients experienced any adverse events secondary to the therapy. In conclusion, we recommend that topical selenium sulfide be added to the therapeutic armamentarium for congenital or acquired hyperkeratosis-particularly for those patients with involvement of their palms and soles.

A uniform method for the simultaneous blood group phenotyping of Fya , Fyb , Jka , Jkb , S, sÌ , P1, k applying lateral-flow technique.

BACKGROUND AND OBJECTIVES: A lateral flow assay for simultaneous blood group typing of ABO, RhD, C, E, c, e, Cw and K with stable end-point and without centrifugation is in routine use since several years (MDmulticard® ). The typing of extended phenotype parameters belonging to the Duffy, Kidd, MNSs blood group systems and others, however, has not yet been demonstrated for this technique. Reliable detection of Fyx , a weak Fyb phenotype with a pronounced quantitative reduction of the number of Fyb antigens on the erythrocyte surface, remains a weakness of current serological blood grouping techniques. MATERIAL AND METHODS: The performance characteristics of the following reagents were evaluated in donor and patient samples in lateral flow technology (MDmulticard® ): Anti-Fya , -Fyb , -Jka , -Jkb , -S, -s̅, -P1 and -k. The sensitivity to detect Fyx was in addition evaluated with Fyx positive samples, which had been preselected by MALDI-TOF MS-based genotyping. RESULTS: All results obtained with the MDmulticard® were in full accordance with those of the CE-certified reference products for all the eight reagent formulations used: Anti-Fya , -Fyb , -Jka , -Jkb , -S, -s̅, -P1 and -k. Also, all Fyx phenotypes of the selected population of 93 positive samples, originally identified by MALDI-TOF MS-based genotyping, were reliably detected by the lateral flow assay. CONCLUSION: Extended phenotype blood group parameters, including the serologically challenging Fyx phenotype, can be determined simultaneously, rapidly and accurately using the lateral flow (MDmulticard® ) technology, even in cases when IgG class antibodies are the only source of diagnostic antibodies.

Wound Healing Devices Brief Vignettes.

Significance: The demand for wound care therapies is increasing. New wound care products and devices are marketed at a dizzying rate. Practitioners must make informed decisions about the use of medical devices for wound healing therapy. This paper provides updated evidence and recommendations based on a review of recent publications. Recent Advances: The published literature on the use of medical devices for wound healing continues to support the use of hyperbaric oxygen therapy, negative pressure wound therapy, and most recently electrical stimulation. Critical Issue: To inform wound healing practitioners of the evidence for or against the use of medical devices for wound healing. This information will aid the practitioner in deciding which technology should be accepted or rejected for clinical use. Future Directions: To produce high quality, randomized controlled trials or acquire outcome-based registry databases to further test and improve the knowledge base as it relates to the use of medical devices in wound care.

First Report of Rhizoctonia spp. Causing a Root Rot of the Invasive Rangeland Weed Lepidium draba in North America.

The exotic, invasive perennial rangeland weed Lepidium draba spreads rapidly and reduces native species diversity. The extensive root system of L. draba constitutes 76% of its biomass (4). Thus, searches have been done for biocontrol agents that target root tissue or that may interact with a weevil, Ceutorhynchus assimilis, that causes galls in the crown area of L. draba. An association of Rhizoctonia spp. with root tissue of plants galled by the weevil has been documented in Europe (3). The possible presence of soilborne pathogens similar to those found in the native range has been the subject of L. draba surveys in the United States. One such survey in 2008 detected a few plants with reddened and chlorotic foliage in a stand near Shepherd, MT. Such symptoms typically indicate the occurrence of soilborne diseases on L. draba in the native range of the weed (2). The site had shown a gradual increase in the range of detectable pathogens beginning with foliar pathogens in 1997. In 2010, at the Shepherd site, L. draba plants with similar (but more severe) symptoms to those seen in 2008 were noted in a different area of the stand. Excavation of the roots in both years revealed brown, sunken crown and root cankers. Pieces of root tissue were excised from the lesions and plated on acidified PDA and Ko and Hora medium. A non-sporulating fungus was isolated from three plants. Colonies of the isolates on PDA were typical of known Rhizoctonia spp. The 2010 isolates were determined to be multinucleate using DAPI and were paired with 14 tester (including subgroups) isolates of AG-1 to AG-4 on water agar. Anastomosis was observed between the multinucleate isolates and the AG-2-1 tester isolate. Sequence analysis of ITS of the rDNA of a multinucleate isolate (GenBank KJ545577) indicated 99% similarity with an accession of R. solani AG 2-1 (AB547381). The 2008 isolates were binucleate. A binucleate isolate, KJ545578, had 100% similarity with an isolate of Rhizoctonia spp. AG-A (AY927356). Pathogenicity tests consisted of planting 6-week-old seedlings of L. draba, one per pot, in ten 85-cm-diameter pots of pasteurized soil mix infested with Rhizoctonia-colonized barley grain that had been dried and milled. An inoculum level of ~8 CFU/g (1) of air-dried soil was established by most probable number calculations from fourfold dilutions of infested soil. Controls were the same number of plants in pasteurized potting mix. Results were recorded after 3 months in a greenhouse at 20-25°C. The test was repeated. Typically, R. solani caused mortality of six to eight plants, from which it was re-isolated, whereas binuclate isolates caused stunting and lower dry weight of L. draba. Control plants remained asymptomatic. This is the first report of R. solani and binucleate Rhizoctonia spp. on L. draba in North America. References: (1) A. J. Caesar et al. Plant Dis. 93:1350, 2009. (2) A. J. Caesar et al. Biol. Control 52:140, 2010. (3) A. J. Caesar et al. Plant Dis. 96:145, 2011. (4) R. F. Miller et al. Agronomy J. 86:487, 1994.