Nonlinear optics of fibre event horizons.

The nonlinear interaction of light in an optical fibre can mimic the physics at an event horizon. This analogue arises when a weak probe wave is unable to pass through an intense soliton, despite propagating at a different velocity. To date, these dynamics have been described in the time domain in terms of a soliton-induced refractive index barrier that modifies the velocity of the probe.

Developing clinical guidelines: how much rigour is required?

Clinical guidelines that are rigorously developed play a fundamental role in improving healthcare and reducing unnecessary variations in practice. National guidelines are increasingly used by healthcare professionals, patients and commissioners; however, national bodies are unable to meet the demand for guidance on all topics. There are fewer resources available for guidance produced locally or by specialty groups, and it is necessary to achieve a balance between pragmatism and rigour while conforming to the widely accepted norms of what constitutes a good guideline.

Clinical audit: still an important tool for improving healthcare.

The use of data to challenge and improve healthcare has a long and distinguished history but has often failed to bring about expected improvements. It has never become fully embedded in clinical practice, probably because data alone are insufficient to drive change. There is now a greater appreciation that changing and improving healthcare requires changing behaviours.

Experimental dynamics of Akhmediev breathers in a dispersion varying optical fiber.

We investigate experimentally the dynamics of Akhmediev breathers in an optical fiber with a longitudinally tailored dispersion that allows to nearly freeze the breather evolution near their point of maximal compression. Our results are in good agreement with numerical simulations.

The behavioural response of mice lacking NK₁ receptors to guanfacine resembles its clinical profile in treatment of ADHD.

Background And Purpose: Mice with functional ablation of substance P-preferring neurokinin-1 receptors (NK1R-/- mice) display behavioural abnormalities resembling those in attention deficit hyperactivity disorder (ADHD). Here, we investigated whether the ADHD treatment, guanfacine, alleviated the hyperactivity and impulsivity/inattention displayed by NK1R-/- mice in the light/dark exploration box (LDEB) and 5-choice serial reaction-time task (5-CSRTT), respectively. Following reports of co-morbid anxiety in ADHD, we also investigated effects of guanfacine on anxiety-like behaviour displayed by NK1R-/- and wild-type (WT) mice in the elevated plus maze (EPM).

ERAD and how viruses exploit it.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes.

Disease risk factors identified through shared genetic architecture and electronic medical records.

Genome-wide association studies have identified genetic variants for thousands of diseases and traits. We evaluated the relationships between specific risk factors (for example, blood cholesterol level) and diseases on the basis of their shared genetic architecture in a comprehensive human disease-single-nucleotide polymorphism association database (VARIMED), analyzing the findings from 8962 published association studies. Similarity between traits and diseases was statistically evaluated on the basis of their association with shared gene variants.

Spatiotemporal structure of femtosecond Bessel beams from spatial light modulators.

We numerically investigate the spatiotemporal structure of Bessel beams generated with spatial light modulators (SLMs). Grating-like phase masks enable the spatial filtering of undesired diffraction orders produced by SLMs. Pulse front tilt and temporal broadening effects are investigated.

On Hokusai's : localization, linearity and a rogue wave in sub-Antarctic waters.

The Hokusai woodcut entitled has been interpreted as an unusually large storm wave, likely to be classed as a rogue wave, and possibly generated from nonlinear wave dynamics (J. H. E.

Far-detuned mid-infrared frequency conversion via normal dispersion modulation instability in chalcogenide microwires.

We report the observation of modulation instability (MI) in the mid-infrared (mid-IR) spectral region by pumping a hybrid polymer-chalcogenide optical microwire with a femtosecond optical parametric oscillator operating at 2.6 μm. It is further shown that this MI occurs in the normal dispersion regime through negative fourth-order dispersion and leads to far-detuned parametric frequency conversion at 2 and 3.

Tumor cellularity as a quality assurance measure for accurate clinical detection of BRAF mutations in melanoma.

Background: Detection of BRAF mutations is an established standard of care to predict small-molecule inhibitor (vemurafenib) response in metastatic melanoma. Molecular assays should be designed to detect not only the most common p.V600E mutation, but also p.

Automated detection of off-label drug use.

Off-label drug use, defined as use of a drug in a manner that deviates from its approved use defined by the drug's FDA label, is problematic because such uses have not been evaluated for safety and efficacy. Studies estimate that 21% of prescriptions are off-label, and only 27% of those have evidence of safety and efficacy. We describe a data-mining approach for systematically identifying off-label usages using features derived from free text clinical notes and features extracted from two databases on known usage (Medi-Span and DrugBank).

Translational Bioinformatics Approaches to Drug Development.

Significance: A majority of therapeutic interventions occur late in the pathological process, when treatment outcome can be less predictable and effective, highlighting the need for new precise and preventive therapeutic development strategies that consider genomic and environmental context. Translational bioinformatics is well positioned to contribute to the many challenges inherent in bridging this gap between our current reactive methods of healthcare delivery and the intent of , particularly in the areas of drug development, which forms the focus of this review.

Recent Advances: A variety of powerful informatics methods for organizing and leveraging the vast wealth of available molecular measurements available for a broad range of disease contexts have recently emerged.

Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence.

Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders.

The "medical neighborhood": integrating primary and specialty care for ambulatory patients.

As health care organizations create larger networks, better coordination of primary and specialty care is paramount. Attention has focused on strengthening primary care by creating patient-centered medical homes. The "medical neighborhood" provides a framework for structured, reciprocal relationships that integrate specialty care and extend the principles of the medical home to all practicing physicians.

The 2-implant maxillary overdenture: a clinical report.

Maxillary implant overdentures present a number of different challenges in comparison to the established and predictable benefits of mandibular implant overdentures. This report highlights the lack of evidence and conflicting findings in the maxillary implant overdenture literature and presents a clinical treatment of a 2-implant and subsequently 1-implant maxillary overdenture with reduced palatal coverage.

STORMSeq: an open-source, user-friendly pipeline for processing personal genomics data in the cloud.

The increasing public availability of personal complete genome sequencing data has ushered in an era of democratized genomics. However, read mapping and variant calling software is constantly improving and individuals with personal genomic data may prefer to customize and update their variant calls. Here, we describe STORMSeq (Scalable Tools for Open-Source Read Mapping), a graphical interface cloud computing solution that does not require a parallel computing environment or extensive technical experience.

Unifying immunology with informatics and multiscale biology.

The immune system is a highly complex and dynamic system. Historically, the most common scientific and clinical practice has been to evaluate its individual components. This kind of approach cannot always expose the interconnecting pathways that control immune-system responses and does not reveal how the immune system works across multiple biological systems and scales.

First trimester exposure to antiretroviral therapy and risk of birth defects.

Background: Use of antiretroviral (ARV) drugs during pregnancy has been associated with an increased risk of birth defects, but the evidence remains inconclusive.

Methods: We identified infants born to human immunodeficiency virus (HIV)-infected mothers between 1994 and 2009 using Tennessee Medicaid data linked to vital records. Maternal HIV status was based on diagnosis codes, prescriptions for ARVs and HIV-related laboratory testing.

Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease.

Background & Aims: Very early onset inflammatory bowel diseases (VEOIBD), including infant disorders, are a diverse group of diseases found in children younger than 6 years of age. They have been associated with several gene variants. Our aim was to identify the genes that cause VEOIBD.

Dent's disease complicated by an acute Budd-Chiari syndrome.

We present the case of a young boy with Dent's disease, identified as having a mutation in the kidney-specific chloride-proton antitransporter CLCN5 during investigation for nephrotic-range proteinuria. He went on to develop growth hormone deficiency and was treated with recombinant growth hormone. He later presented acutely with hepatorenal failure and thrombotic occlusion of the middle and right hepatic veins consistent with a diagnosis of Budd-Chiari syndrome, which required a prolonged period of intensive care.