A qualitative exploration of children's lives with rare diseases.

Background: Rare diseases encompass a diverse group of debilitating and sometimes life-threatening conditions that affect a small percentage of the population, posing a significant public health challenge. Despite their rarity, around 70% of these diseases afflict children, yet limited research has focused on their experiences. This study aimed to gain insights into the day-to-day challenges children living with rare diseases face.

UCL MotionInput: Touchless computing interactions in clinical training, radiology and operating theatres.

Coupled with advances to federated on-device computer vision, the convenience of use and ease of access of cameras integrated into existing computers and tablets will increase touchless computing uptake in the form of gesture recognition software in healthcare for both clinicians and patients.

Children and young people's experiences of living with rare diseases: An integrative review.

Problem: Rare diseases are any disease affecting fewer than five people in 10,000. More than 8000 rare diseases and 50-75% of all rare diseases affect children. The purpose of this review was to critically appraise and synthesize existing literature relating to the impact of rare diseases on children's day-to-day lives.

Nudging within learning health systems: next generation decision support to improve cardiovascular care.

The increasing volume and richness of healthcare data collected during routine clinical practice have not yet translated into significant numbers of actionable insights that have systematically improved patient outcomes. An evidence-practice gap continues to exist in healthcare. We contest that this gap can be reduced by assessing the use of nudge theory as part of clinical decision support systems (CDSS).

Making the invisible visible: New perspectives on the intersection of human-environment interactions of clinical teams in intensive care.

Understanding human behaviour is essential to the successful adoption of new technologies, and for the promotion of safer care. This requires capturing the detail of clinical workflows to inform the design of new human-technology interactions. We are interested particularly in the possibilities for touchless technologies that can decipher human speech, gesture and motion and allow for interactions that are free of contact.

Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland.

Since 1972, 18 patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal-onset maple syrup urine disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical, and IQ data. A fourth cluster comprised of two early childhood deaths; a third patient died as an adult.

Expanding the genetic and phenotypic spectrum of branched-chain amino acid transferase 2 deficiency.

The first step in branched-chain amino acid (BCAA) catabolism is catalyzed by the two BCAA transferase isoenzymes, cytoplasmic branched-chain amino acid transferase (BCAT) 1, and mitochondrial BCAT2. Defects in the second step of BCAA catabolism cause maple syrup urine disease (MSUD), a condition which has been far more extensively investigated. Here, we studied the consequences of BCAT2 deficiency, an ultra-rare condition in humans.

A blended design approach for pervasive healthcare: bringing together users, experts and technology.

Pervasive healthcare is beginning to investigate how novel sensory technologies can be used to measure body movements and provide various forms of feedback. This position paper reflects on a blended design approach that uses a combination of technology inspiration, consultation with experts and user-centred design for the development of a personalized pervasive healthcare system to support stroke rehabilitation.

Genomic and functional adaptation in surface ocean planktonic prokaryotes.

The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.

Widespread divergence between incipient Anopheles gambiae species revealed by whole genome sequences.

The Afrotropical mosquito Anopheles gambiae sensu stricto, a major vector of malaria, is currently undergoing speciation into the M and S molecular forms. These forms have diverged in larval ecology and reproductive behavior through unknown genetic mechanisms, despite considerable levels of hybridization. Previous genome-wide scans using gene-based microarrays uncovered divergence between M and S that was largely confined to gene-poor pericentromeric regions, prompting a speciation-with-ongoing-gene-flow model that implicated only about 3% of the genome near centromeres in the speciation process.

Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line.

We have identified new genomic alterations in the breast cancer cell line HCC1954, using high-throughput transcriptome sequencing. With 120 Mb of cDNA sequences, we were able to identify genomic rearrangement events leading to fusions or truncations of genes including MRE11 and NSD1, genes already implicated in oncogenesis, and 7 rearrangements involving other additional genes. This approach demonstrates that high-throughput transcriptome sequencing is an effective strategy for the characterization of genomic rearrangements in cancers.

Outcomes of siblings with classical galactosemia.

Objectives: To determine the long-term outcome of dietary intervention in siblings from 14 Irish families with classical galactosemia (McKusick 230400), an autosomal recessive disorder of carbohydrate metabolism and galactose-1-phosphate uridyltransferase (GALT) deficiency.

Study Design: Outcomes in siblings on dietary galactose restriction were studied to evaluate whether birth order (ie, time of commencement of diet) and compliance with lactose-restricted diet (galactose intake > or < 20 mg /day), assessed by dietary recall and biochemical monitoring of galactose-1-phosphate [Gal-1-P] and galactitol values, affected outcomes. The outcome variables assessed were IQ, speech, and language assessment scores, neurologic examination results, and magnetic resonance imaging (MRI) of the brain.

Emerging DNA sequencing technologies for human genomic medicine.

The completion of draft sequences of the human genome represented a remarkable achievement for automated DNA sequencing based on Sanger technology. However, the future requires substantial leaps in sequencing technology such that whole genome sequencing will become a standard component of biomedical research and patient care. In this review we describe current advances that are in early stages of development, but that point toward technology that will enable the onset of genomic medicine encompasses strategies for preventative medicine and intervention based on complete knowledge of an individual's genome.

New molecular reporters for rapid protein folding assays.

The GFP folding reporter assay uses a C-terminal GFP fusion to report on the folding success of upstream fused polypeptides. The GFP folding assay is widely-used for screening protein variants with improved folding and solubility, but truncation artifacts may arise during evolution, i.e.

Evolution of genes and genomes on the Drosophila phylogeny.

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution.

The diploid genome sequence of an individual human.

Presented here is a genome sequence of an individual human. It was produced from approximately 32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region.

Genome sequence of Aedes aegypti, a major arbovirus vector.

We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements.

Evolutionary and biomedical insights from the rhesus macaque genome.

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.

The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific.

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.

A Sanger/pyrosequencing hybrid approach for the generation of high-quality draft assemblies of marine microbial genomes.

Since its introduction a decade ago, whole-genome shotgun sequencing (WGS) has been the main approach for producing cost-effective and high-quality genome sequence data. Until now, the Sanger sequencing technology that has served as a platform for WGS has not been truly challenged by emerging technologies. The recent introduction of the pyrosequencing-based 454 sequencing platform (454 Life Sciences, Branford, CT) offers a very promising sequencing technology alternative for incorporation in WGS.

Neonatal neurodevelopmental outcomes following tocolysis with glycerol trinitrate patches.

Objective: The object of this study was to determine the effects of maternal tocolysis with glycerol trinitrate (GTN) patches on the neurodevelopment of infants.

Study Design: This was a randomized, multicenter, controlled trial comparing the efficacy of GTN patches with standard beta2 agonist as tocolytic therapy. The previously reported outcomes of this study indicated no difference in neonatal mortality or morbidity to hospital discharge.