Programmable-trajectory ultrafast flying focus pulses.

"Flying focus" techniques produce laser pulses with dynamic focal points that travel distances much greater than a Rayleigh length. The implementation of these techniques in laser-based applications requires the design of optical configurations that can both extend the focal range and structure the radial group delay. This article describes a method for designing optical configurations that produce ultrashort flying focus pulses with programmable-trajectory focal points. The method is illustrated by several examples that employ an axiparabola for extending the focal range and either a reflective echelon or a deformable mirror-spatial light modulator pair for structuring the radial group delay. The latter configuration enables rapid exploration and optimization of flying foci, which could be ideal for experiments.

A phospho-dawn of protein modification anticipates light onset in the picoeukaryote Ostreococcus tauri.

Diel regulation of protein levels and protein modification had been less studied than transcript rhythms. Here, we compare transcriptome data under light-dark cycles with partial proteome and phosphoproteome data, assayed using shotgun MS, from the alga Ostreococcus tauri, the smallest free-living eukaryote. A total of 10% of quantified proteins but two-thirds of phosphoproteins were rhythmic. Mathematical modelling showed that light-stimulated protein synthesis can account for the observed clustering of protein peaks in the daytime. Prompted by night-peaking and apparently dark-stable proteins, we also tested cultures under prolonged darkness, where the proteome changed less than under the diel cycle. Among the dark-stable proteins were prasinophyte-specific sequences that were also reported to accumulate when O. tauri formed lipid droplets. In the phosphoproteome, 39% of rhythmic phospho-sites reached peak levels just before dawn. This anticipatory phosphorylation suggests that a clock-regulated phospho-dawn prepares green cells for daytime functions. Acid-directed and proline-directed protein phosphorylation sites were regulated in antiphase, implicating the clock-related casein kinases 1 and 2 in phase-specific regulation, alternating with the CMGC protein kinase family. Understanding the dynamic phosphoprotein network should be facilitated by the minimal kinome and proteome of O. tauri. The data are available from ProteomeXchange, with identifiers PXD001734, PXD001735, and PXD002909.

Erratum: Dephasingless Laser Wakefield Acceleration [Phys. Rev. Lett. 124, 134802 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.124.134802.

"Let's take that [stop sign] down." Provider perspectives on barriers to and opportunities for PrEP prescription to African American girls and young women in Alabama.

HIV disproportionately impacts many groups, including Black adolescent girls and young women (AGYW) aged 13-24 living in the Deep South. Current prevention efforts have the potential to further exacerbate disparities within this population as HIV pre-exposure prophylaxis (PrEP) remains underutilized by Black AGYW in the South. We conducted in-depth interviews (IDIs) grounded in Andersen's Model of Healthcare Utilization exploring providers' PrEP prescribing practices to Black AGYW in Alabama. Eleven providers completed IDIs exploring providers' PrEP prescription knowledge and experiences. Cross-cutting themes included: (1) Community and provider-level stigmas (including those propagated by legislation) relating to HIV and sexuality limit sexual health discussions with Black AGYW clients; (2) Low PrEP knowledge and comfort with guidelines limits PrEP conversations and reinforces low uptake and prescriptions; (3) Healthcare systems and structural barriers impede PrEP access for youth. Multi-level (structural, community, and provider) barriers to PrEP prescription demands high activation energy for providers to prescribe PrEP. We present recommendations in training in sexual health assessment, updates to PrEP guidelines to accommodate risk assessment appropriate for AGYW, and increased implementation science focused on PrEP prescription for Black AGYW in order to reduce HIV incidence for this population.

Presence of DNA from Chlamydia-like organisms in the nasal cavities of grey seal pups (Halichoerus grypus) and three different substrates present in a breeding colony.

BACKGROUND: Chlamydia-like organisms (CLO) have been found to be present in many environmental niches, including human sewage and agricultural run-off, as well as in a number of aquatic species worldwide. Therefore, monitoring their presence in sentinel wildlife species may be useful in assessing the wider health of marine food webs in response to habitat loss, pollution and disease. We used nasal swabs from live (n = 42) and dead (n = 50) pre-weaned grey seal pups and samples of differing natal substrates (n = 8) from an off-shore island devoid of livestock and permanent human habitation to determine if CLO DNA is present in these mammals and to identify possible sources. RESULTS: We recovered CLO DNA from 32/92 (34.7%) nasal swabs from both live (n = 17) and dead (n = 15) seal pups that clustered most closely with currently recognised species belonging to three chlamydial families: Parachlamydiaceae (n = 22), Rhabdochlamydiaceae (n = 6), and Simkaniaceae (n = 3). All DNA positive sediment samples (n = 7) clustered with the Rhabdochlamydiaceae. No difference was found in rates of recovery of CLO DNA in live versus dead pups suggesting the organisms are commensal but their potential as opportunistic secondary pathogens could not be determined. CONCLUSION: This is the first report of CLO DNA being found in marine mammals. This identification warrants further investigation in other seal populations around the coast of the UK and in other areas of the world to determine if this finding is unique or more common than shown by this data. Further investigation would also be warranted to determine if they are present as purely commensal organisms or whether they could also be opportunistic pathogens in seals, as well as to investigate possible sources of origin, including whether they originated as a result of anthropogenic impacts, including human waste and agricultural run-off.

Dephasingless Laser Wakefield Acceleration.

Laser wakefield accelerators (LWFAs) produce extremely high gradients enabling compact accelerators and radiation sources but face design limitations, such as dephasing, occurring when trapped electrons outrun the accelerating phase of the wakefield. Here we combine spherical aberration with a novel cylindrically symmetric echelon optic to spatiotemporally structure an ultrashort, high-intensity laser pulse that can overcome dephasing by propagating at any velocity over any distance. The ponderomotive force of the spatiotemporally shaped pulse can drive a wakefield with a phase velocity equal to the speed of light in vacuum, preventing trapped electrons from outrunning the wake. Simulations in the linear regime and scaling laws in the bubble regime illustrate that this dephasingless LWFA can accelerate electrons to high energies in much shorter distances than a traditional LWFA-a single 4.5 m stage can accelerate electrons to TeV energies without the need for guiding structures.

Large-scale bleaching of corals on the Great Barrier Reef.

In 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching. In the southern hemisphere summer of March-April 2016, we used aerial surveys to measure the level of bleaching on 1,156 individual reefs throughout the 2,300 km length of the Great Barrier Reef, the world's largest coral reef system. The accuracy of the aerial scores was ground-truthed with detailed underwater surveys of bleaching at 260 sites (104 reefs), allowing us to compare aerial and underwater bleaching data with satellite-derived temperatures and with associated model predictions of bleaching. The severity of bleaching on individual reefs in 2016 was tightly correlated with the level of local heat exposure: the southernmost region of the Great Barrier Reef escaped with only minor bleaching because summer temperatures there were close to average. Gradients in nutrients and turbidity from inshore to offshore across the Great Barrier Reef had minimal effect on the severity of bleaching. Similarly, bleaching was equally severe on reefs that are open or closed to fishing, once the level of satellite-derived heat exposure was accounted for. The level of post-bleaching mortality, measured underwater after 7-8 months, was tightly correlated with the aerial scores measured at the peak of bleaching. Similarly, reefs with a high aerial bleaching score also experienced major shifts in species composition due to extensive mortality of heat-sensitive species. Reefs with low bleaching scores did not change in composition, and some showed minor increases in coral cover. Two earlier mass bleaching events occurred on the Great Barrier Reef in 1998 and 2002, that were less severe than 2016. In 2016, <9% of scored reefs had no bleaching, compared to 42% in 2002 and 44% in 1998. Conversely, the proportion of reefs that were severely bleached (>60% of corals affected) was four times higher in 2016. The geographic footprint of each of the three events is distinctive, and matches satellite-derived sea surface temperature patterns. Our aerial surveys indicate that past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. This data set of aerial bleaching scores provides a historical baseline for comparison with future bleaching events. No copyright restrictions apply to the use of this data set other than citing this publication.

Network analyses reveal novel aspects of ALS pathogenesis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons, muscle atrophy and paralysis. Mutations in the human VAMP-associated protein B (hVAPB) cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. Modifiers cluster in a diverse array of biological functions including processes and genes that have been previously linked to hVAPB function, such as proteolysis and vesicular trafficking. In addition to established mechanisms, the screen identified endocytic trafficking and genes controlling proliferation and apoptosis as potent modifiers of ALS8-mediated defects. Surprisingly, the list of modifiers was mostly enriched for proteins linked to lipid droplet biogenesis and dynamics. Computational analysis reveals that most modifiers can be linked into a complex network of interacting genes, and that the human genes homologous to the Drosophila modifiers can be assembled into an interacting network largely overlapping with that in flies. Identity markers of the endocytic process were also found to abnormally accumulate in ALS patients, further supporting the relevance of the fly data for human biology. Collectively, these results not only lead to a better understanding of hVAPB function but also point to potentially relevant targets for therapeutic intervention.

Realising the rhetoric: refreshing public health providers' efforts to honour Te Tiriti o Waitangi in New Zealand.

OBJECTIVES: New Zealand has a unique tool, Te Tiriti o Waitangi, the Treaty of Waitangi, for addressing health disparities. Indigenous Maori have compromised health status compared to other groups. This paper investigates ways in which public health units (PHUs) and non-governmental organisations (NGOs) use Te Tiriti o Waitangi in service delivery to Maori. DESIGN: A nationwide telephone survey of primary health providers (n=162) was conducted in 2014-15. Participants were asked about effectiveness and monitoring of their service delivery to Maori. RESULTS: PHUs reported actively working with Maori, and Te Tiriti o Waitangi to reduce health disparities. Direct Maori engagement with development and delivery of programmes was viewed as essential. Strategies included designated PHU staff in positions of responsibility, formal partnerships with Maori, and providing operational and strategic guidance. Some PHUs supported development of cultural competencies. NGO responsiveness to Maori was variable. Some NGOs described prioritising service delivery and programmes for Maori. Others reported the focus of their service was European or other non-Maori ethnicities. Lack of resources or past difficulties engaging with Maori were barriers. CONCLUSION: Public health has an ethical commitment to reduce health disparities. Advancing Te Tiriti obligations in everyday practice has the potential to address inequalities.

Analysis of compound heterozygotes reveals that the mouse floxed Pax6 (tm1Ued) allele produces abnormal eye phenotypes.

Analysis of abnormal phenotypes produced by different types of mutations has been crucial for our understanding of gene function. Some floxed alleles that retain a neomycin-resistance selection cassette (neo cassette) are not equivalent to wild-type alleles and provide useful experimental resources. Pax6 is an important developmental gene and the aim of this study was to determine whether the floxed Pax6 (tm1Ued) (Pax6 (fl) ) allele, which has a retained neo cassette, produced any abnormal eye phenotypes that would imply that it differs from the wild-type allele. Homozygous Pax6 (fl/fl) and heterozygous Pax6 (fl/+) mice had no overt qualitative eye abnormalities but morphometric analysis showed that Pax6 (fl/fl) corneas tended be thicker and smaller in diameter. To aid identification of weak effects, we produced compound heterozygotes with the Pax6 (Sey-Neu) (Pax6 (-)) null allele. Pax6 (fl/-) compound heterozygotes had more severe eye abnormalities than Pax6 (+/-) heterozygotes, implying that Pax6 (fl) differs from the wild-type Pax6 (+) allele. Immunohistochemistry showed that the Pax6 (fl/-) corneal epithelium was positive for keratin 19 and negative for keratin 12, indicating that it was abnormally differentiated. This Pax6 (fl) allele provides a useful addition to the existing Pax6 allelic series and this study demonstrates the utility of using compound heterozygotes with null alleles to unmask cryptic effects of floxed alleles.

The reduced kinome of Ostreococcus tauri: core eukaryotic signalling components in a tractable model species.

BACKGROUND: The current knowledge of eukaryote signalling originates from phenotypically diverse organisms. There is a pressing need to identify conserved signalling components among eukaryotes, which will lead to the transfer of knowledge across kingdoms. Two useful properties of a eukaryote model for signalling are (1) reduced signalling complexity, and (2) conservation of signalling components. The alga Ostreococcus tauri is described as the smallest free-living eukaryote. With less than 8,000 genes, it represents a highly constrained genomic palette. RESULTS: Our survey revealed 133 protein kinases and 34 protein phosphatases (1.7% and 0.4% of the proteome). We conducted phosphoproteomic experiments and constructed domain structures and phylogenies for the catalytic protein-kinases. For each of the major kinases families we review the completeness and divergence of O. tauri representatives in comparison to the well-studied kinomes of the laboratory models Arabidopsis thaliana and Saccharomyces cerevisiae, and of Homo sapiens. Many kinase clades in O. tauri were reduced to a single member, in preference to the loss of family diversity, whereas TKL and ABC1 clades were expanded. We also identified kinases that have been lost in A. thaliana but retained in O. tauri. For three, contrasting eukaryotic pathways - TOR, MAPK, and the circadian clock - we established the subset of conserved components and demonstrate conserved sites of substrate phosphorylation and kinase motifs. CONCLUSIONS: We conclude that O. tauri satisfies our two central requirements. Several of its kinases are more closely related to H. sapiens orthologs than S. cerevisiae is to H. sapiens. The greatly reduced kinome of O. tauri is therefore a suitable model for signalling in free-living eukaryotes.

The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons.

In neurogenesis, neural cell fate specification is generally triggered by proneural transcription factors. Whilst the role of proneural factors in fate specification is well studied, the link between neural specification and the cellular pathways that ultimately must be activated to construct specialised neurons is usually obscure. High-resolution temporal profiling of gene expression reveals the events downstream of atonal proneural gene function during the development of Drosophila chordotonal (mechanosensory) neurons. Among other findings, this reveals the onset of expression of genes required for construction of the ciliary dendrite, a key specialisation of mechanosensory neurons. We determine that atonal activates this cellular differentiation pathway in several ways. Firstly, atonal directly regulates Rfx, a well-known highly conserved ciliogenesis transcriptional regulator. Unexpectedly, differences in Rfx regulation by proneural factors may underlie variations in ciliary dendrite specialisation in different sensory neuronal lineages. In contrast, fd3F encodes a novel forkhead family transcription factor that is exclusively expressed in differentiating chordotonal neurons. fd3F regulates genes required for specialized aspects of chordotonal dendrite physiology. In addition to these intermediate transcriptional regulators, we show that atonal directly regulates a novel gene, dilatory, that is directly associated with ciliogenesis during neuronal differentiation. Our analysis demonstrates how early cell fate specification factors can regulate structural and physiological differentiation of neuronal cell types. It also suggests a model for how subtype differentiation in different neuronal lineages may be regulated by different proneural factors. In addition, it provides a paradigm for how transcriptional regulation may modulate the ciliogenesis pathway to give rise to structurally and functionally specialised ciliary dendrites.

Consolidation and translation regulation.

mRNA translation, or protein synthesis, is a major component of the transformation of the genetic code into any cellular activity. This complicated, multistep process is divided into three phases: initiation, elongation, and termination. Initiation is the step at which the ribosome is recruited to the mRNA, and is regarded as the major rate-limiting step in translation, while elongation consists of the elongation of the polypeptide chain; both steps are frequent targets for regulation, which is defined as a change in the rate of translation of an mRNA per unit time. In the normal brain, control of translation is a key mechanism for regulation of memory and synaptic plasticity consolidation, i.e., the off-line processing of acquired information. These regulation processes may differ between different brain structures or neuronal populations. Moreover, dysregulation of translation leads to pathological brain function such as memory impairment. Both normal and abnormal function of the translation machinery is believed to lead to translational up-regulation or down-regulation of a subset of mRNAs. However, the identification of these newly synthesized proteins and determination of the rates of protein synthesis or degradation taking place in different neuronal types and compartments at different time points in the brain demand new proteomic methods and system biology approaches. Here, we discuss in detail the relationship between translation regulation and memory or synaptic plasticity consolidation while focusing on a model of cortical-dependent taste learning task and hippocampal-dependent plasticity. In addition, we describe a novel systems biology perspective to better describe consolidation.

Improved prediction of hiking speeds using a data driven approach.

Hikers and hillwalkers typically use the gradient in the direction of travel (walking slope) as the main variable in established methods for predicting walking time (via the walking speed) along a route. Research into fell-running has suggested further variables which may improve speed algorithms in this context; the gradient of the terrain (hill slope) and the level of terrain obstruction. Recent improvements in data availability, as well as widespread use of GPS tracking now make it possible to explore these variables in a walking speed model at a sufficient scale to test statistical significance. We tested various established models used to predict walking speed against public GPS data from almost 88,000 km of UK walking / hiking tracks. Tracks were filtered to remove breaks and non-walking sections. A new generalised linear model (GLM) was then used to predict walking speeds. Key differences between the GLM and established rules were that the GLM considered the gradient of the terrain (hill slope) irrespective of walking slope, as well as the terrain type and level of terrain obstruction in off-road travel. All of these factors were shown to be highly significant, and this is supported by a lower root-mean-square-error compared to existing functions. We also observed an increase in RMSE between the GLM and established methods as hill slope increases, further supporting the importance of this variable.

Routine EGFR and KRAS Mutation analysis using COLD-PCR in non-small cell lung cancer.

Aims: Epidermal growth factor receptor (EGFR) antagonists are particularly active in non-small cell lung cancer (NSCLC) patients with tumours bearing mutations in the EFGR gene. EGFR mutation prevalence is very low in squamous histology. Response rates using these drugs in patients with KRAS mutations are low, so available KRAS mutation information may aid treatment selection in the second-line setting. Since 2009, patients presenting to this hospital with non-squamous histology have been routinely screened for mutations in both the EGFR and KRAS genes, with results used to inform treatment. We present an analysis of 215 consecutive patients for whom EGFR mutation analysis was informative. Methodology: EGFR and KRAS mutations were identified using a COLD-PCR technique confirmed with sequencing, which makes no prior assumption about location of specific mutations. Results were correlated with clinical and demographic data from hospital records, where available. Results: The prevalence of patients with EGFR mutations was 14% and for KRAS mutations it was 27%. Despite the conventional understanding that EGFR and KRAS mutations are mutually exclusive, we identified two dual mutations. Of 29 patients identified with mutated EGFR, there were 3/8/8/10 mutations in exons 18/19/20/21 respectively. Exon 20 mutations were identified in a proportion exceeding many other series because of the unbiased mutation analysis used, and clinical benefit was seen in some of these. Of 23 different EGFR mutations identified, 11 have not previously been described in the literature. Conclusions: The high prevalence of EGFR, KRAS or both mutations (40%) in this non-squamous population tested in clinical practice supports a policy of routine screening for these mutations in NSCLC.

A multi-tiered intervention to address behavioural and cognitive changes after diagnosis of primary brain tumour: a feasibility study.

PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour (PBT) can result in challenging behaviours (CBs), with limited documentation on treatment approaches. This study explored the feasibility of employing a Behavioural Consultancy approach to manage CBs, targeting individuals with PBT, family and treating staff. METHODS: Participants were patients and families of two hospitals and health professionals from cancer/neurological services. A single-case experimental design piloted skill-based training and environmental changes in managing socio-behavioural impairments in a person with a low grade astrocytoma. A half-day workshop to train family members (n = 7) in compensatory strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was provided to 43 health professionals in managing CBs after PBT. For both workshops, a pre-post impact evaluation was conducted employing a purpose-designed Strategies Use Measure. RESULTS: All three interventions demonstrated positive results. The single case showed a 71% decrease in the target behaviour (time spent talking) post-intervention. Some attrition to these gains was observed at two follow-up time points (3 and 5 months). Participants from both workshops demonstrated significant post-intervention increases in perceived knowledge of Strategy Use (family members z = 2.03, p < 0.05; health professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These initial studies highlight the potential of employing an integrated multi-tiered intervention based on a Behavioural Consultancy model to manage CBs after PBT.

SFARI genes and where to find them; modelling Autism Spectrum Disorder specific gene expression dysregulation with RNA-seq data.

Autism Spectrum Disorders (ASD) have a strong, yet heterogeneous, genetic component. Among the various methods that are being developed to help reveal the underlying molecular aetiology of the disease one approach that is gaining popularity is the combination of gene expression and clinical genetic data, often using the SFARI-gene database, which comprises lists of curated genes considered to have causative roles in ASD when mutated in patients. We build a gene co-expression network to study the relationship between ASD-specific transcriptomic data and SFARI genes and then analyse it at different levels of granularity. No significant evidence is found of association between SFARI genes and differential gene expression patterns when comparing ASD samples to a control group, nor statistical enrichment of SFARI genes in gene co-expression network modules that have a strong correlation with ASD diagnosis. However, classification models that incorporate topological information from the whole ASD-specific gene co-expression network can predict novel SFARI candidate genes that share features of existing SFARI genes and have support for roles in ASD in the literature. A statistically significant association is also found between the absolute level of gene expression and SFARI's genes and Scores, which can confound the analysis if uncorrected. We propose a novel approach to correct for this that is general enough to be applied to other problems affected by continuous sources of bias. It was found that only co-expression network analyses that integrate information from the whole network are able to reveal signatures linked to ASD diagnosis and novel candidate genes for the study of ASD, which individual gene or module analyses fail to do. It was also found that the influence of SFARI genes permeates not only other ASD scoring systems, but also lists of genes believed to be involved in other neurodevelopmental disorders.

Comparison of rule- and ordinary differential equation-based dynamic model of DARPP-32 signalling network.

Dynamic modelling has considerably improved our understanding of complex molecular mechanisms. Ordinary differential equations (ODEs) are the most detailed and popular approach to modelling the dynamics of molecular systems. However, their application in signalling networks, characterised by multi-state molecular complexes, can be prohibitive. Contemporary modelling methods, such as rule- based (RB) modelling, have addressed these issues. The advantages of RB modelling over ODEs have been presented and discussed in numerous reviews. In this study, we conduct a direct comparison of the time courses of a molecular system founded on the same reaction network but encoded in the two frameworks. To make such a comparison, a set of reactions that underlie an ODE model was manually encoded in the Kappa language, one of the RB implementations. A comparison of the models was performed at the level of model specification and dynamics, acquired through model simulations. In line with previous reports, we confirm that the Kappa model recapitulates the general dynamics of its ODE counterpart with minor differences. These occur when molecules have multiple sites binding the same interactor. Furthermore, activation of these molecules in the RB model is slower than in the ODE one. As reported for other molecular systems, we find that, also for the DARPP-32 reaction network, the RB representation offers a more expressive and flexible syntax that facilitates access to fine details of the model, easing model reuse. In parallel with these analyses, we report a refactored model of the DARPP-32 interaction network that can serve as a canvas for the development of more complex dynamic models to study this important molecular system.

Creation and evaluation of full-text literature-derived, feature-weighted disease models of genetically determined developmental disorders.

There are >2500 different genetically determined developmental disorders (DD), which, as a group, show very high levels of both locus and allelic heterogeneity. This has led to the wide-spread use of evidence-based filtering of genome-wide sequence data as a diagnostic tool in DD. Determining whether the association of a filtered variant at a specific locus is a plausible explanation of the phenotype in the proband is crucial and commonly requires extensive manual literature review by both clinical scientists and clinicians. Access to a database of weighted clinical features extracted from rigorously curated literature would increase the efficiency of this process and facilitate the development of robust phenotypic similarity metrics. However, given the large and rapidly increasing volume of published information, conventional biocuration approaches are becoming impractical. Here, we present a scalable, automated method for the extraction of categorical phenotypic descriptors from the full-text literature. Papers identified through literature review were downloaded and parsed using the Cadmus custom retrieval package. Human Phenotype Ontology terms were extracted using MetaMap, with 76-84% precision and 65-73% recall. Mean terms per paper increased from 9 in title + abstract, to 68 using full text. We demonstrate that these literature-derived disease models plausibly reflect true disease expressivity more accurately than widely used manually curated models, through comparison with prospectively gathered data from the Deciphering Developmental Disorders study. The area under the curve for receiver operating characteristic (ROC) curves increased by 5-10% through the use of literature-derived models. This work shows that scalable automated literature curation increases performance and adds weight to the need for this strategy to be integrated into informatic variant analysis pipelines. Database URL: https://doi.org/10.1093/database/baac038.

Erratum to 'Feasibility of a two-part person-centred care initiative for people living with dementia in acute hospitals: A mixed method study' International Journal of Nursing Studies Advances, 3 (2021) Article Number: 100040.

[This corrects the article DOI: 10.1016/j.ijnsa.2021.100040.].