South Pacific Convergence Zone dynamics, variability and impacts in a changing climate

The South Pacific Convergence Zone (SPCZ) is a diagonal band of intense rainfall and deep atmospheric convection extending from the equator to the subtropical South Pacific. Displacement of the SPCZ causes variability in rainfall, tropical-cyclone activity and sea level that affects South Pacific island populations and surrounding ecosystems. In this Review, we synthesize recent advances in understanding the physical mechanisms responsible for the SPCZ location and orientation, its interactions with the principal drivers of tropical climate variability, regional and global effects of the SPCZ and its response to anthropogenic climate change. Emerging insight is beginning to provide a coherent description of the character and variability of the SPCZ over synoptic, intraseasonal, interannual and longer timescales. For example, the diagonal orientation of the SPCZ and its natural variability are both the result of a subtle chain of interactions between the tropical and extratropical atmosphere, forced and modulated by the underlying sea surface temperature gradients. However, persistent biases in, and deficiencies of, existing models limit confidence in future projections. Improved climate models and new methods for regional modelling might better constrain future SPCZ projections, aiding climate change adaptation and planning among vulnerable South Pacific communities

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Debunking Challenges to Moral Realism

<p>Heightened awareness of the evolutionary, socio-cultural, and psychological origins of our moral judgments pushes many of us in the direction of moral skepticism, in the direction of doubting the objective truth of our moral judgments. But should awareness of the origins of our moral judgments shake our confidence in them? Are there good moral debunking challenges or debunking arguments from premises concerning the accessible origins of our moral judgments to skeptical conclusions regarding them? In vigorous pursuit of these questions, this dissertation sifts three promising moral debunking challenges to moral realism, namely Richard Joyce's (2001) evolutionary debunking argument from epistemic insensitivity, Sharon Street's (2006) "Darwinian Dilemma," and David Enoch's (2010) "Epistemological Challenge." It is argued that each challenge faces cogent objections that not only demonstrate the inadequacy of the best debunking challenges available but also instructively guide us to the development of new and more forceful debunking challenges to moral realism. This dissertation develops two new and forceful debunking challenges, both of which target the epistemic reliability and justification of our moral judgments on realist views of the moral facts. The first new debunking challenge starts from the premise that the best explanation of our moral judgments does not appeal to their truth and invokes a new species of epistemic insensitivity to secure the conclusion that our moral belief-forming processes are epistemically unreliable. The second new debunking challenge reasons that the best explanation of the fact that moral realists have no good explanation of the reliability of our moral belief-forming processes is that there is no such reliability.</p>Dissertatio

AI Case Studies: Potential for Human Health, Space Exploration and Colonisation and a Proposed Superimposition of the Kubler-Ross Change Curve on the Hype Cycle

The development and deployment of artificial intelligence (AI) is and will profoundly reshape human society, the culture and the composition of civilisations which make up human kind. All technological triggers tend to drive a hype curve which over time is realised by an output which is often unexpected, taking both pessimistic and optimistic perspectives and actions of drivers, contributors and enablers on a journey where the ultimate destination may be unclear. In this paper we hypothesise that this journey is not dissimilar to the personal journey described by the Kubler-Ross change curve and illustrate this by commentary on the potential of AI for drug discovery, development and healthcare and as an enabler for deep space exploration and colonisation. Recent advances in the call for regulation to ensure development of safety measures associated with machine-based learning are presented which, together with regulation of the rapidly emerging digital after-life industry, should provide a platform for realising the full potential benefit of AI for the human species