AI Through Ethical Lenses: A Discourse Analysis of Guidelines for AI in Healthcare.

While the technologies that enable Artificial Intelligence (AI) continue to advance rapidly, there are increasing promises regarding AI's beneficial outputs and concerns about the challenges of human-computer interaction in healthcare. To address these concerns, institutions have increasingly resorted to publishing AI guidelines for healthcare, aiming to align AI with ethical practices. However, guidelines as a form of written language can be analyzed to recognize the reciprocal links between its textual communication and underlying societal ideas. From this perspective, we conducted a discourse analysis to understand how these guidelines construct, articulate, and frame ethics for AI in healthcare. We included eight guidelines and identified three prevalent and interwoven discourses: (1) AI is unavoidable and desirable; (2) AI needs to be guided with (some forms of) principles (3) trust in AI is instrumental and primary. These discourses signal an over-spillage of technical ideals to AI ethics, such as over-optimism and resulting hyper-criticism. This research provides insights into the underlying ideas present in AI guidelines and how guidelines influence the practice and alignment of AI with ethical, legal, and societal values expected to shape AI in healthcare.

One R or the other - an experimental bioethics approach to 3R dilemmas in animal research.

Sacrificial dilemmas such as the trolley problem play an important role in experimental philosophy (x-phi). But it is increasingly argued that, since we are not likely to encounter runaway trolleys in our daily life, the usefulness of such thought experiments for understanding moral judgments in more ecologically valid contexts may be limited. However, similar sacrificial dilemmas are experienced in real life by animal research decision makers. As part of their job, they must make decisions about the suffering, and often the death, of many non-human animals. For this reason, a context-specific investigation of so-called "3R dilemmas" (i.e., dilemmas where there is a conflict between the principles of replacement, reduction, and refinement of the use of animals in research) is essential to improve the situation of both non-human animals and human stakeholders. An approach well suited for such investigation is experimental philosophical bioethics ("bioxphi"), which draws on methods similar to x-phi to probe more realistic, practical scenarios with an eye to informing normative debates and ethical policy. In this article, we argue for a need to investigate 3R dilemmas among professional decision-makers using the tools of bioxphi. In a first step, we define 3R dilemmas and discuss previous investigations of professionals' attitudes in such cases. In a second step, we show how bioxphi is a promising method to investigate the whys and hows of professional decision-making in 3R dilemmas. In a last step, we provide a bioxphi template for 3R dilemmas, give recommendations on its use, explore the normative relevance of data collected by such means, and discuss important limitations.

Natural killer cell subset count and antigen-stimulated activation in response to exhaustive running following adaptation to a ketogenic diet.

NEW FINDINGS: What is the central question of this study? Does a ketogenic diet (KD) modulate circulating counts of natural killer (NK) cells, including CD56bright and CD56dim subsets, and their ability to activate (CD69 expression) following in vitro antigen stimulation in response to exhaustive moderate-intensity exercise? What is the main finding and its importance? The KD amplified the biphasic exercise-induced NK cell response due to a greater mobilisation of the cytotoxic CD56dim subset but did not alter NK cell CD69 expression. The KD appears to modulate exercise-induced circulating NK cell mobilisation and egress, but not antigen-stimulated circulating NK cell activation. ABSTRACT: We investigated the effect of a 31-day ketogenic diet (KD) compared with a habitual, carbohydrate (CHO)-based diet on total circulating natural killer (NK) CD3- CD56+ , dim and bright subset count, and antigen-stimulated CD3- CD56+ cell activation (CD69+ ) in response to exhaustive running. In a randomised, repeated-measures, cross-over study, eight trained, male endurance athletes ingested a 31-day low-CHO KD or their habitual diet (HD). On day 31, participants ran to exhaustion at 70% V ̇ O 2 max $\dot{V}_{{\rm{O}}_{2}{\rm{max}}}$ (∼3.5-4 h, ∼45-50 km). A low-CHO (<10 g) meal was ingested prior to the KD trial, with fat ingested during exercise. A high-CHO (2 g kg-1 ) meal was ingested prior to the HD trial, with CHO (∼55 g h-1 ) ingested during exercise. Venous blood samples were collected at pre-exercise, post-exercise and 1 h post-exercise. The KD amplified the classical exercise-induced biphasic CD3- CD56+ cell response by increasing the post-exercise counts (P = 0.0004), which appeared to be underpinned by the cytotoxic CD3- CD56dim subset (main effect of time point, P < 0.0001). The KD had no effect on NK cells' expression of CD69 or their geometric mean fluorescence intensity of CD69 expression, either for unstimulated or for antigen-stimulated NK cells (all P > 0.05). In conclusion, adaptation to a KD may alter the number of circulating NK cells but not their ability to activate to an antigenic challenge.

The effect of a 2 week ketogenic diet, versus a carbohydrate-based diet, on cognitive performance, mood and subjective sleepiness during 36 h of extended wakefulness in military personnel: An exploratory study.

Extended wakefulness, or sleep deprivation, impairs cognitive performance and brain glucose metabolism. A ketogenic diet (KD) provides an alternative fuel source, ketone bodies, that could elicit a metabolic benefit during sleep deprivation. A randomised, cross-over trial was conducted with seven male military personnel. Participants ingested an iso-energetic ketogenic diet or carbohydrate-based diet for 14 days, immediately followed by 36 h of extended wakefulness and separated by a 12 day washout. Cognitive performance, mood, subjective sleepiness, capillary blood glucose, and D-ß-hydroxybutyrate concentrations were measured every 2 h during extended wakefulness. Linear mixed models were used to analyse data. D-ß-hydroxybutyrate was higher (p < 0.001) and glucose was lower (p < 0.01) on the KD compared with the carbohydrate-based diet. The KD improved psychomotor vigilance task performance (number of lapses, mean reciprocal response time, mean fastest 10% response time (RT), and mean slowest 10% RT; all p < 0.05), running memory continuous performance test performance (RT and number of correct responses per minute; both p < 0.01), and vigour, fatigue, and sleepiness (all, p ≤ 0.001) compared with the carbohydrate-based diet. In conclusion, a KD demonstrated beneficial effects on cognitive performance, mood, and sleepiness during 36 h of extended wakefulness compared with a carbohydrate-based diet.

Integrating physiological monitoring systems in military aviation: a brief narrative review of its importance, opportunities, and risks.

Military pilots risk their lives during training and operations. Advancements in aerospace engineering, flight profiles, and mission demands may require the pilot to test the safe limits of their physiology. Monitoring pilot physiology (e.g. heart rate, oximetry, and respiration) inflight is in consideration by several nations to inform pilots of reduced performance capacity and guide future developments in aircraft and life-support system design. Numerous challenges, however, prevent the immediate operationalisation of physiological monitoring sensors, particularly their unreliability in the aerospace environment and incompatibility with pilot clothing and protective equipment. Human performance and behaviour are also highly variable and measuring these in controlled laboratory settings do not mirror the real-world conditions pilots must endure. Misleading or erroneous predictive models are unacceptable as these could compromise mission success and lose operator trust. This narrative review provides an overview of considerations for integrating physiological monitoring systems within the military aviation environment.Practitioner summary: Advancements in military technology can conflictingly enhance and compromise pilot safety and performance. We summarise some of the opportunities, limitations, and risks of integrating physiological monitoring systems within military aviation. Our intent is to catalyse further research and technological development.Abbreviations: AGS: anti-gravity suit; AGSM: anti-gravity straining manoeuvre; A-LOC: almost loss of consciousness; CBF: cerebral blood flow; ECG: electrocardiogram; EEG: electroencephalogram; fNIRS: functional near-infrared spectroscopy; G-forces: gravitational forces; G-LOC: gravity-induced loss of consciousness; HR: heart rate; HRV: heart rate variability; LSS: life-support system; NATO: North Atlantic Treaty Organisation; PE: Physiological Episode; PCO2: partial pressure of carbon dioxide; PO2: partial pressure of oxygen; OBOGS: on board oxygen generating systems; SpO2: peripheral blood haemoglobin-oxygen saturation; STANAG: North Atlantic Treaty Organisation Standardisation Agreement; UPE: Unexplained Physiological Episode; WBV: whole body vibration.

Adaptation to a ketogenic diet modulates adaptive and mucosal immune markers in trained male endurance athletes.

This study examined the effect of short-term adaptation to a ketogenic diet (KD) on resting and post-exercise immune markers. Using a randomized, repeated-measures, crossover design, eight trained, male, endurance athletes ingested a 31-day low carbohydrate (CHO), KD (energy intake: 4% CHO; 78% fat) or their habitual diet (HD) (energy intake: 43% CHO; 38% fat). On days 0 and 31, participants ran to exhaustion at 70% VO2max . A high-CHO (2 g·kg-1 ) meal was ingested prior to the pre-HD, post-HD, and pre-KD trials, with CHO (~55 g·h-1 ) ingested during exercise, whereas a low-CHO (<10 g) meal was ingested prior to the post-KD trial, with fat ingested during exercise. Blood and saliva samples were collected at pre-exercise, exhaustion, and 1 hour post-exhaustion. T-cell-related cytokine gene expression within peripheral blood mononuclear cells (PBMCs) and whole-blood inflammatory cytokine production were determined using 24-hour multi-antigen-stimulated whole-blood cultures. Multi-antigen-stimulated PBMC IFN-γ mRNA expression and the IFN-γ/IL-4 mRNA expression ratio were higher at exhaustion in the post-KD compared with pre-KD trial (P = 0.003 and P = 0.004); however, IL-4 and IL-10 mRNA expression were unaltered (P > 0.05). Multi-antigen-stimulated whole-blood IL-10 production was higher in the post-KD compared with pre-KD trial (P = 0.028), whereas IL-1ß, IL-2, IL-8, and IFN-γ production was lower in the post-HD compared with pre-HD trial (P < 0.01). Salivary immunoglobulin A (SIgA) secretion rate was higher in the post-KD compared with pre-KD trial (P < 0.001). In conclusion, short-term adaptation to a KD in endurance athletes may alter the pro- and anti-inflammatory immune cell cytokine response to a multi-antigen in vitro and SIgA secretion rate.

Predictors of upper respiratory tract symptom risk: Differences between elite rugby union and league players.

This study examined possible predictors of upper respiratory tract symptom (URTS) episodes in elite rugby union and league players (n = 51) during intensive pre-season training. Baseline saliva and blood samples were collected in the first week of pre-season training for analysis of salivary secretory immunoglobulin A (SIgA) and cytomegalovirus. Thereafter, SIgA, URTS, internal training load and self-reported wellness data were repeatedly measured throughout a 10-week pre-season training period. Univariate frailty model analysis, which included 502 observations, was performed for each rugby code for the following independent predictor variables: SIgA concentration, internal training load, total wellness, sleep quantity, sleep quality and stress. Rugby union and league players experienced a similar number of URTS episodes; however, predictors of URTS episodes differed between the codes. No biomarkers or self-reported measures significantly predicted URTS risk in rugby union players, while reductions in self-reported total wellness (HR: 0.731, p = 0.004) and sleep quality (HR: 0.345, p = 0.001) predicted increased URTS risk in rugby league players. The findings from this study highlight that factors influencing URTS risk are perhaps sport specific and this may be attributed to different sporting demands and/or different management of players by team-practitioners.

Advance Car-Crash Planning: Shared Decision Making between Humans and Autonomous Vehicles.

In this article we summarise some previously described proposals for ethical governance of autonomous vehicles ('smart cars'), critique them, and offer an alternative solution. Rather than programming cars to react to crash situations in the same way as humans, having humans program pre-set responses for a wide range of different potential scenarios, or applying particular ethical theories, we suggest that decisions should be made jointly between humans and cars. Given that humans lack the requisite processing capacity, and computers lack the necessary ethical capacity, the medical paradigm of advance care planning can be retooled for this new context. Advance car-crash planning provides a way to combine humans' ethical preferences with the advanced data processing capacities of computers to enable shared decision making in collision situations.

The Cost of Coronavirus Obligations: Respecting the Letter and Spirit of Lockdown Regulations.

We all now know that the novel coronavirus is anything but a common cold. The pandemic has created many new obligations for all of us, several of which come with serious costs to our quality of life. But in some cases, the guidance and the law are open to a degree of interpretation, leaving us to decide what is the ethical (or unethical but desired) course of action. Because of the high cost of some of the obligations, a conflict of interest can arise between what we want to do and what it is right to do. And so, some people choose to respect only the letter of the law, but not the spirit, or not to respect even the spirit of the guidelines. This paper identifies and describes the new obligations imposed on us all by the pandemic, considers their costs in terms of the good life, and provides an ethical analysis of two personal and two public cases in terms of the letter and spirit of the guidance and legislation.

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines.

A one-flask, two-step procedure from 3-amino-2-methyl-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one affords the Streptomyces secondary metabolites legonmycins A and B - three operations overall from methyl N-Boc-prolinate. The key step proceeds in each case via N,O-diacylation, then selective oxidative hydrolysis of the intermediate bicyclic pyrrole and establishes a precedent for the synthesis of related C(7a)-hydroxylated pyrrolizidines.

(Side) effects of the rule of the road and neurophysiology on traffic safety: A hypothesis.

Nowadays, the roots of left-hand traffic (LHT) and right-hand traffic (RHT) - including fighting on horse-back and whipping horses that are drawing carriages - are at an all-time low; thus, it is time to assess and appreciate the nexus of road-safety practices and human neurophysiology. We hypothesize that safety of LHT and RHT can be associated with neurophysiology. We summarize scattered empirical research into plausible links between neurophysiological aspects such as handedness, eye movement bias, and hemispheric lateralisation and how safe, in theory, LHT vs. RHT may be for whom. The scarcity and limitations of empirical data into road traffic accidents associated with LHT or RHT are surprising. Even though it was claimed that countries with LHT have lower collision rates than countries with RHT some 50 years ago, we lack informative analyses of traffic accidents in countries with either LHT or RHT which consider plausibly associated neurophysiology. Overall, we predict that LHT (with the driver sitting on the right) is safer than RHT. As 'the rule of the road' and neurophysiology may have important unrecognized "side" effects, we suggest that (and how) this rationale should be tested.

Acute hyperketonaemia alters T-cell-related cytokine gene expression within stimulated peripheral blood mononuclear cells following prolonged exercise.

PURPOSE: We investigated the effect of the racemic ß-hydroxybutyrate precursor, R,S-1,3-butanediol (BD), on T-cell-related cytokine gene expression within stimulated peripheral blood mononuclear cells (PBMC) following prolonged, strenuous exercise. METHODS: A repeated-measures, randomised, crossover study was conducted in nine healthy, trained male cyclists (age, 26.7 ± 5.2 years; VO2peak, 63.9 ± 2.5 mL kg-1 min-1). Participants ingested 0.35 g kg-1 of BD or placebo 30 min before and 60 min during 85 min of steady-state (SS) exercise, which preceded a ~ 30 min time-trial (TT) (7 kJ kg-1). Blood samples were collected at pre-supplement, pre-exercise, post-SS, post-TT and 1-h post-TT. Whole blood cultures were stimulated with Staphylococcal enterotoxin B (SEB) for 24 h to determine T-cell-related interleukin (IL)-4, IL-10 and interferon (IFN)-γ mRNA expression within isolated PBMCs in vitro. RESULTS: Serum cortisol, total circulating leukocyte and lymphocyte, and T-cell subset concentrations were similar between trials during exercise and recovery (all p > 0.05). BD ingestion increased T-cell-related IFN-γ mRNA expression compared with placebo throughout exercise and recovery (p = 0.011); however, IL-4 and IL-10 mRNA expression and the IFN-γ/IL-4 mRNA expression ratio were unaltered (all p > 0.05). CONCLUSION: Acute hyperketonaemia appears to transiently amplify the initiation of the pro-inflammatory T-cell-related IFN-γ response to an immune challenge in vitro during and following prolonged, strenuous exercise; suggesting enhanced type-1 T-cell immunity at the gene level.

The side effects of deemed consent: changing defaults in organ donation.

In this Current Controversy article, I describe and analyse the imminent move to a system of deemed consent for deceased organ donation in England and similar planned changes in Scotland, in light of evidence from Wales, where the system changed in 2015. Although the media has tended to focus on the potential benefits and ethical issues relating to the main change from an opt-in default to an opt-out one, other defaults will also change, while some will remain the same. Interaction of these other defaults with the principal one raise several ethical issues that may complicate efforts to use deemed consent to increase donation rates. Most significantly, changing the main default will have the effect of changing the default for patients' families, who play a vital role in the consent process.

The Effect of 1,3-Butanediol on Cycling Time-Trial Performance.

This study investigated the effect of the racemic ß-hydroxybutyrate (ßHB) precursor, R,S-1,3-butanediol (BD), on time-trial (TT) performance and tolerability. A repeated-measures, randomized, crossover study was conducted in nine trained male cyclists (age, 26.7 ± 5.2 years; body mass, 69.6 ± 8.4 kg; height, 1.82 ± 0.09 m; body mass index, 21.2 ± 1.5 kg/m2; VO2peak,63.9 ± 2.5 ml·kg-1·min-1; Wmax, 389.3 ± 50.4 W). Participants ingested 0.35 g/kg of BD or placebo 30 min before and 60 min during 85 min of steady-state exercise, which preceded a ∼25- to 35-min TT (i.e., 7 kJ/kg). The ingestion of BD increased blood D-ßHB concentration throughout exercise (0.44-0.79 mmol/L) compared with placebo (0.11-0.16 mmol/L; all p < .001), which peaked 1 hr following the TT (1.38 ± 0.35 vs. 0.34 ± 0.24 mmol/L; p < .001). Serum glucose and blood lactate concentrations were not different between trials (all p > .05). BD ingestion increased oxygen consumption and carbon dioxide production after 20 min of steady-state exercise (p = .002 and p = .032, respectively); however, no further effects on cardiorespiratory parameters were observed. Within the BD trial, moderate to severe gastrointestinal symptoms were reported in five participants, and low levels of dizziness, nausea, and euphoria were reported in two participants. However, this had no effect on TT duration (placebo, 28.5 ± 3.6 min; BD, 28.7 ± 3.2 min; p = .62) and average power output (placebo, 290.1 ± 53.7 W; BD, 286.4 ± 45.9 W; p = .50). These results suggest that BD has no benefit for endurance performance.

T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise.

Strenuous exercise bouts and heavy training are associated with a heightened anti-inflammatory state and a transient suppression of several immune components. In turn, many athletes are susceptible to illness, particularly upper respiratory symptoms (e.g. cough, sore throat, running nose). T-lymphocytes (T-cells) are important for orchestrating the immune response and can be categorised into subsets according to their phenotypical characteristics resulting from polarisation (i.e. type-1, type-2 and regulatory T-cells). Each T-cell subset has a unique functional role, including their capacity to produce pro- and anti-inflammatory cytokines in response to an immune challenge. Prolonged and exhaustive exercise typically reduces peripheral blood type-1 T-cell number and their capacity to produce the pro-inflammatory cytokine, interferon-γ. Moreover, heavy training loads are associated with elevated numbers of resting peripheral blood type-2 and regulatory T-cells, which characteristically produce the anti-inflammatory cytokines, interleukin-4 and interleukin-10, respectively. This appears to increase the risk of upper respiratory symptoms, potentially due to the cross-regulatory effect of interleukin-4 on interferon-γ production and immunosuppressive action of IL-10. Catecholamines significantly influence the number of peripheral blood T-cells in response to exercise. Whereas, glucocorticoids and prostaglandin E2 promote the production of anti-inflammatory cytokines by T-cells. In summary, strenuous exercise bouts and heavy training shifts T-cell immunity towards an anti-inflammatory state. This impairs the ability of the immune system to mount an inflammatory response to an immune challenge, which may weaken defences against intracellular pathogens (e.g. viruses), and increase the risk of infection and viral reactivation.

Positive HIV Test Results from Deceased Organ Donors: Should We Disclose to Next of Kin?

In the context of deceased organ donation, donors are routinely tested for HIV, to check for suitability for organ donation. This article examines whether a donor's HIV status should be disclosed to the donor's next of kin. On the one hand, confidentiality requires that sensitive information not be disclosed, and a duty to respect confidentiality may persist after death. On the other hand, breaching confidentiality may benefit third parties at risk of having been infected by the organ donor, as it may permit them to be tested for HIV and seek treatment in case of positive results. We conclude that the duty to warn third parties surpasses the duty to respect confidentiality. However, in order to minimize risks linked to the breach of confidentiality, information should be restrained to only concerned third parties, that is, those susceptible to having been infected by the donor.

Gatekeepers of Reward: a Pilot Study on the Ethics of Editing and Competing Evaluations of Value.

The reward infrastructure in science centres on publication, in which journal editors play a key role. Reward distribution hinges on value assessments performed by editors, who draw from plural value systems to judge manuscripts. This conceptual paper examines the numerous biases and other factors that affect editorial decisions. Hybrid and often conflicting value systems contribute to an infrastructure in which editors manage reward through editorial review, commissioned commentaries and reviews and weighing of peer review judgments. Taken together, these systems and processes push the editor into a role resembling censorship. Editors and authors both experience this phenomenon as an unintended side-effect of the reward infrastructure in science. To work towards a more constructive editor-author relationship, we propose a conversation, an exchange between editor and author in which value is collectively assessed (or constructed) as obligatory passage points in the publishing process are traversed. This paper contributes to the discourse on editorial practices by problematising editorial paradigms in a new way and suggesting solutions to entrenched problems.

Controlled Donation After Circulatory Determination of Death.

Controlled donation after circulatory determination of death (cDCDD) concerns donation after withdrawal of life-sustaining therapy (W-LST). We examine the ethical issues raised by W-LST in the cDCDD context in the light of a review of cDCDD protocols and the ethical literature. Our analysis confirms that W-LST procedures vary considerably among cDCDD centers and that despite existing recommendations, the conflict of interest in the W-LST decision and process might be difficult to avoid, the process of W-LST might interfere with usual end-of-life care, and there is a risk of hastening death. In order to ensure that the practice of W-LST meets already well-established ethical recommendations, we suggest that W-LST should be managed in the ICU by an ICU physician who has been part of the W-LST decision. Recommending extubation for W-LST, when this is not necessarily the preferred procedure, is inconsistent with the recommendation to follow usual W-LST protocol. As the risk of conflicts of interest in the decision of W-LST and in the process of W-LST exists, this should be acknowledged and disclosed. Finally, when cDCDD programs interfere with W-LST and end-of-life care, this should be transparently disclosed to the family, and specific informed consent is necessary.

The Consequences of Vagueness in Consent to Organ Donation.

In this article I argue that vagueness concerning consent to post-mortem organ donation causes considerable harm in several ways. First, the information provided to most people registering as organ donors is very vague in terms of what is actually involved in donation. Second, the vagueness regarding consent to donation increases the distress of families of patients who are potential organ donors, both during and following the discussion about donation. Third, vagueness also increases the chances that the patient's intention to donate will not be fulfilled due to the family's distress. Fourth, the consequent reduction in the number of donated organs leads to avoidable deaths and increased suffering among potential recipients, and distresses them and their families. There are three strategies which could be used to reduce the harmful effects of this vagueness. First, recategorizing the reasons (commonly referred to as 'overrules' under the current system) given by families who refuse donation from registered donors would bring greater clarity to donation discussions. Second, people who wish to donate their organs should be encouraged to discuss their wishes in detail with their families, and to consider recording their wishes in other ways. Finally, the consent system for organ donation could be made more detailed, ensuring both that more information is provided to potential donors and that they have more flexibility in how their intentions are indicated; this last strategy, however, could have the disadvantage of discouraging some potential donors from registering.

Practical Considerations in Donation After Circulatory Determination of Death in Switzerland.

Faced with similar issues of organ scarcity to its neighbors, Switzerland has developed donation after circulatory determination of death (DCDD) as a way to expand the organ pool since 1985. Here, we analyze the history, practical considerations, and ethical issues relating to the Swiss donation after circulatory death programs. In Switzerland, determination of death for DCDD requires a stand-off period of 10 minutes. This time between cardiac arrest and the declaration of death is mandated in the guidelines of the Swiss Academy of Medical Sciences. As in other DCDD programs, safeguards are put to avoid physicians denying lifesaving treatment to savable patients because of being influenced by receivers' interest. An additional recommendation could be made: Recipients should be transparently informed of the worse graft outcomes with DCDD programs and given the possibility to refuse such organs.