Moral enhancement and cheapened achievement: Psychedelics, virtual reality and AI.

A prominent critique of cognitive or athletic enhancement claims that certain performance-improving drugs or technologies may 'cheapen' resulting achievements. Considerably less attention has been paid to the impact of enhancement on the value of moral achievements. Would the use of moral enhancement (bio)technologies, rather than (solely) 'traditional' means of moral development like schooling and socialization, cheapen the 'achievement' of morally improving oneself? We argue that, to the extent that the 'cheapened achievement' objection succeeds in the domains of cognitive or athletic enhancement, it could plausibly also succeed in the domain of moral enhancement-but only regarding certain forms.

The Key Features of a Genetic Nondiscrimination Policy: A Delphi Consensus Statement.

Importance: Governments worldwide have become increasingly cognizant of the spread of genetic discrimination (negative treatment or harm on the basis of actual or presumed genetic characteristics). Despite efforts by a number of governments to establish regulations addressing this phenomenon, public concern about genetic discrimination persists.

Objective: To identify key elements of an optimal genetic nondiscrimination policy and inform policymakers as they seek to allay genetic nondiscrimination and related public anxieties.

A proposal for an inclusive working definition of genetic discrimination to promote a more coherent debate.

Genetic discrimination is an evolving phenomenon that impacts fundamental human rights such as dignity, justice and equity. Although, in the past, various definitions to better conceptualize genetic discrimination have been proposed, these have been unable to capture several key facets of the phenomenon. In this Perspective, we explore definitions of genetic discrimination across disciplines, consider criticisms of such definitions and show how other forms of discrimination and stigmatization can compound genetic discrimination in a way that affects individuals, groups and systems.

Using curiosity to render the invisible, visible.

Virtues commonly associated with physicians and other healthcare professionals include empathy, respect, kindness, compassion, trustworthiness, and many more. Building upon the work of Bortolloti, Murphy-Hollies, and others, I suggest that curiosity as a virtue has an integral role to play in healthcare, namely, in helping to make those who are invisible, visible. Practicing the virtue of curiosity enables one to engage with and explore the experiences of patients and contributes toward building a physician-patient relationship of trust.

The carryover effects of embryonic incubation temperature on subsequent growth and thermal tolerance in white sturgeon.

Environmental variation experienced during early periods of development can lead to persistent phenotypic alteration, known as carryover effects. Such effects increase concern for threatened or endangered species such as the white sturgeon (Acipenser transmontanus), particularly considering expected thermal changes due to climate change. We evaluated how temperature during embryonic development affects physiological parameters such as larval and early juvenile growth and thermal tolerance.

Valuing the Acute Subjective Experience.

Psychedelics, including psilocybin, and other consciousness-altering compounds such as 3,4-methylenedioxymethamphetamine (MDMA), currently are being scientifically investigated for their potential therapeutic uses, with a primary focus on measurable outcomes: for example, alleviation of symptoms or increases in self-reported well-being. Accordingly, much recent discussion about the possible value of these substances has turned on estimates of the magnitude and duration of persisting positive effects in comparison to harms. However, many have described the value of a psychedelic experience with little or no reference to such therapeutic benefits, instead seeming to find the experience valuable in its own right.

Defusing the legal and ethical minefield of epigenetic applications in the military, defense, and security context.

Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers' health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers' minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality.

A role for kindness and curiosity in healthcare.

In his paper 'Ethical problems with kindness in healthcare', Jesudason sets out an interesting examination of the concept of kindness, arguing that it poses significant ethical challenges due to its discretionary nature. I suggest that kindness, a concept difficult to define, may still have a role to play in healthcare. Different treatments of kindness show us that it need not be discretionary, and that kind care can be provided to all.

Psychedelics, Meaningfulness, and the "Proper Scope" of Medicine: Continuing the Conversation.

Psychedelics such as psilocybin reliably produce significantly altered states of consciousness with a variety of subjectively experienced effects. These include certain changes to perception, cognition, and affect, which we refer to here as the acute subjective effects of psychedelics. In recent years, psychedelics such as psilocybin have also shown considerable promise as therapeutic agents when combined with talk therapy, for example, in the treatment of major depression or substance use disorder.

Cognitive impairment in intensive care unit patients: A pilot mixed-methods feasibility study exploring incidence and experiences for recovering patients.

Background: Despite improvements in survival after critical illness and intensive care unit (ICU) treatment, some recovering patients still face ongoing challenges. There are few investigations exploring the incidence, risk factors, and trajectory for cognitive impairment (CI) in former ICU patients in Australia.

Objectives: To test the feasibility of a study protocol designed to ascertain the incidence and impact of CI during recovery from a critical illness.

Male carriers of the FMR1 premutation show altered hippocampal-prefrontal function during memory encoding.

Previous functional MRI (fMRI) studies have shown that fragile X mental retardation 1 (FMR1) fragile X premutation allele carriers (FXPCs) exhibit decreased hippocampal activation during a recall task and lower inferior frontal activation during a working memory task compared to matched controls. The molecular characteristics of FXPCs includes 55-200 CGG trinucleotide expansions, increased FMR1 mRNA levels, and decreased FMRP levels especially at higher repeat sizes. In the current study, we utilized MRI to examine differences in hippocampal volume and function during an encoding task in young male FXPCs.

Influence of the fragile X mental retardation (FMR1) gene on the brain and working memory in men with normal FMR1 alleles.

The fragile X mental retardation 1 (FMR1) gene plays an important role in the development and maintenance of neuronal circuits that are essential for cognitive functioning. We explored the functional linkage(s) among lymphocytic FMR1 gene expression, brain structure, and working memory in healthy adult males. We acquired T1-weighted and diffusion tensor imaging from 37 males (18-80 years, mean ± SD= 40.

Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation.

Background: The fragile X premutation provides a unique opportunity for the study of genetic and brain mechanisms of behavior and cognition in the context of neurodevelopment and neurodegeneration. Although the neurodegenerative phenotype, fragile X-associated tremor/ataxia syndrome, is well described, evidence of a causal link between the premutation and psychiatric disorder earlier in life, clear delineation of a behavioral/cognitive phenotype, and characterization of the physiological basis of observed symptoms have been elusive.

Methods: We completed functional magnetic resonance imaging targeting the amygdala with an emotion-matching task and concurrent infrared eye tracking, FMR1 molecular genetic testing, and neuropsychological assessment in 23 men with the premutation (mean age = 32.

Health policy analysis: a tool to evaluate in policy documents the alignment between policy statements and intended outcomes.

Objective: Health policy analysis remains surprisingly undeveloped in Australia given the power that policy exercises over the direction of public health. This paper describes the use of a policy analysis tool to evaluate the alignment between policy statements and intended outcomes of principal chronic illness policy documents in New South Wales (NSW) from 1999 to 2008. In doing so, it demonstrates the utility of a set of predefined criteria for use in retrospective policy analysis and potential for use in reviewing policy proposals and making future health policies.

The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1).

A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer.

Dysprosody and stimulus effects in Cantonese speakers with Parkinson's disease.

Background: Dysprosody is a common feature in speakers with hypokinetic dysarthria. However, speech prosody varies across different types of speech materials. This raises the question of what is the most appropriate speech material for the evaluation of dysprosody.

Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).

Hemiasterlin, a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286, an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models.

D-piece modifications of the hemiasterlin analog HTI-286 produce potent tubulin inhibitors.

Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein. Amides derived from proline had potency comparable to HTI-286. Reduction of the carboxylic acid to ketones and alcohols or its conversion to acidic heterocycles also gave potent analogs.