Artificial intelligence projects in healthcare:10 practical tips for success in a clinical environment

There is much discussion concerning ‘digital transformation’ in healthcare and the potential of artificial intelligence (AI) in healthcare systems. Yet it remains rare to find AI solutions deployed in routine healthcare settings. This is in part due to the numerous challenges inherent in delivering an AI project in a clinical environment. In this article, several UK healthcare professionals and academics reflect on the challenges they have faced in building AI solutions using routinely collected healthcare data.These personal reflections are summarised as 10 practical tips. In our experience, these are essential considerations for an AI healthcare project to succeed. They are organised into four phases: conceptualisation, data management, AI application and clinical deployment. There is a focus on conceptualisation, reflecting our view that initial set-up is vital to success. We hope that our personal experiences will provide useful insights to others looking to improve patient care through optimal data use

Suicide Among Aboriginal People in Canada

This report looks at the complex issues that surround Aboriginal suicide in Canad

OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism

A human cytomegalovirus (HCMV) pentameric glycoprotein complex (PC), gH-gL-UL128-UL130-UL131A, is necessary for viral infection of clinically relevant cell types, including epithelial cells, which are important for interhost transmission and disease. We performed genome-wide CRISPR/Cas9 screens of different cell types in parallel to identify host genes specifically required for HCMV infection of epithelial cells. This effort identified a multipass membrane protein, OR14I1, as a receptor for HCMV infection. This olfactory receptor family member is required for HCMV attachment, entry, and infection of epithelial cells and is dependent on the presence of viral PC. OR14I1 is required for AKT activation and mediates endocytosis entry of HCMV. We further found that HCMV infection of epithelial cells is blocked by a synthetic OR14I1 peptide and inhibitors of adenylate cyclase and protein kinase A (PKA) signaling. Identification of OR14I1 as a PC-dependent HCMV host receptor associated with epithelial tropism and the role of the adenylate cyclase/PKA/AKT-mediated signaling pathway in HCMV infection reveal previously unappreciated targets for the development of vaccines and antiviral therapies

Testing the Cenozoic multisite composite δ¹⁸O and δ¹³C curves: new monospecific Eocene records from a single locality, Demerara Rise (Ocean Drilling Program Leg 207)

Until recently, very few high-quality deep ocean sedimentary sections of Eocene age have been available. Consequently, our understanding of Eocene paleoceanography has become heavily reliant on “composite” records patched together from multiple sites in different ocean basins and generated using multiple taxa (potential sources of “local” noise in the global signal). Here we test the reliability of the early to middle Eocene composite δ18O and δ13C stratigraphies (Zachos et al., 2001) by generating new monospecific records in benthic foraminiferal calcite from a single locality, Demerara Rise, in the tropical western Atlantic (Ocean Drilling Program Leg 207). We present new stable isotope correction factors for commonly used Eocene benthic foraminiferal species. We find that interspecies isotopic offsets are constant across the isotopic range, supporting the notion that the inconstant intertaxa offsets reported elsewhere result from mixing species within genera. In general, the δ18O stratigraphy from Demerara Rise supports the validity of the Eocene δ18O composite, while revealing a temporary warming punctuating middle Eocene cooling. This warming may correspond to the so-called “Middle Eocene Climatic Optimum” previously documented in the Southern Ocean. The composite and Demerara Rise records for δ13C differ substantially. By removing the intersite and intertaxa sources of uncertainty in δ13C, we obtain a clearer picture of carbon cycling during the Eocene. Secular change in interocean δ13C gradients through the Eocene reveals that intervals of climatic warmth (especially the early Eocene) are associated with very small water mass ageing gradients

Commensurate and Incommensurate Vortex Lattice Melting in Periodic Pinning Arrays

We examine the melting of commensurate and incommensurate vortex lattices interacting with square pinning arrays through the use of numerical simulations. For weak pinning strength in the commensurate case we observe an order-order transition from a commensurate square vortex lattice to a triangular floating solid phase as a function of temperature. This floating solid phase melts into a liquid at still higher temperature. For strong pinning there is only a single transition from the square pinned lattice to the liquid state. For strong pinning in the incommensurate case, we observe a multi-stage melting in which the interstitial vortices become mobile first, followed by the melting of the entire lattice, consistent with recent imaging experiments. The initial motion of vortices in the incommensurate phase occurs by an exchange process of interstitial vortices with vortices located at the pinning sites. We have also examined the vortex melting behavior for higher matching fields and find that a coexistence of a commensurate pinned vortex lattice with an interstitial vortex liquid occurs while at higher temperatures the entire vortex lattice melts. For triangular arrays at incommensurate fields higher than the first matching field we observe that the initial vortex motion can occur through a novel correlated ring excitation where a number of vortices can rotate around a pinned vortex. We also discuss the relevance of our results to recent experiments of colloidal particles interacting with periodic trap arrays.Comment: 8 figure

Reputation, concessions, and territorial civil war

Barbara Walter’s application of reputation theory to self-determination movements has advanced our understanding of why many separatist movements result in armed conflict. Walter has shown that governments of multi-ethnic societies often respond to territorial disputes with violence to deter similar future demands by other ethnic groups. When governments grant territorial accommodation to one ethnic group, they encourage other ethnic groups to seek similar concessions. However, a number of recent empirical studies casts doubt on the validity of Walter’s argument. We address recent challenges to the efficacy of reputation building in the context of territorial conflicts by delineating the precise scope conditions of reputation theory. First, we argue that only concessions granted after fighting should trigger additional conflict onsets. Second, the demonstration effects should particularly apply to groups with grievances against the state. We then test the observable implications of our conditional argument for political power-sharing concessions. Using a global sample of ethnic groups in 120 states between 1946 and 2013, we find support for our arguments. Our theoretical framework enables us to identify the conditions under which different types of governmental concessions are likely to trigger future conflicts, and thus has important implications for conflict resolution

Convocation

List of performers and performances

Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6

Cleft lip and cleft palate (CLP) are common disorders that occur either as part of a syndrome, where structures other than the lip and palate are affected, or in the absence of other anomalies. Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant disorders characterized by combinations of cleft lip, CLP, lip pits, skin-folds, syndactyly and oral adhesions which arise as the result of mutations in interferon regulatory factor 6 (IRF6). IRF6 belongs to a family of transcription factors that share a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain. To date, mutation analyses have suggested a broad genotype–phenotype correlation in which missense and nonsense mutations occurring throughout IRF6 may cause VWS; in contrast, PPS-causing mutations are highly associated with the DNA-binding domain, and appear to preferentially affect residues that are predicted to interact directly with the DNA. Nevertheless, this genotype–phenotype correlation is based on the analysis of structural models rather than on the investigation of the DNA-binding properties of IRF6. Moreover, the effects of mutations in the protein interaction domain have not been analysed. In the current investigation, we have determined the sequence to which IRF6 binds and used this sequence to analyse the effect of VWS- and PPS-associated mutations in the DNA-binding domain of IRF6. In addition, we have demonstrated that IRF6 functions as a co-operative transcriptional activator and that mutations in the protein interaction domain of IRF6 disrupt this activity