A Clustered Randomized Trial Informing Patients on Dialysis About Their Ability to Donate Organs and Tissues.

Introduction: The transplant waiting list exceeds the number of organs available. One means of increasing the organ pool is to broaden potential donors to include those with chronic diseases.

Research Questions: The study tested the effectiveness of using peer mentors to encourage individuals on dialysis to enroll on an organ donor registry.

Polyion Complex Micelles for Protein Delivery Benefit from Flexible Hydrophobic Spacers in the Binding Group.

Although a range of polymer-protein polyion complex (PIC) micelle systems have been developed in the literature, relatively little attention has been paid to the influence of polymer structure on the assembly, or to the mechanism of disassembly. In this work, Förster resonance energy transfer is used in combination with light sheet fluorescence microscopy and isothermal calorimetry to monitor the formation and stability of PIC micelles with various carboxylic-acid-based binding blocks in MCF-7 cancer spheroid models. All micelles are stable in the presence of free protein, but are unstable in solutions with an ionic strength >200 mm and prone to disassembly at reduced pH.

Three-dimensional covariance-map imaging of molecular structure and dynamics on the ultrafast timescale.

Ultrafast laser pump-probe methods allow chemical reactions to be followed in real time, and have provided unprecedented insight into fundamental aspects of chemical reactivity. While evolution of the electronic structure of the system under study is evident from changes in the observed spectral signatures, information on rearrangement of the nuclear framework is generally obtained indirectly. Disentangling contributions to the signal arising from competing photochemical pathways can also be challenging.

Quantitative and correlative extreme ultraviolet coherent imaging of mouse hippocampal neurons at high resolution.

Microscopy with extreme ultraviolet (EUV) light can provide many advantages over optical, hard x-ray or electron-based techniques. However, traditional EUV sources and optics have large disadvantages of scale and cost. Here, we demonstrate the use of a laboratory-scale, coherent EUV source to image biological samples-mouse hippocampal neurons-providing quantitative phase and amplitude transmission information with a lateral resolution of 80 nm and an axial sensitivity of ~1 nm.

Judging in the genomic era: judges' genetic knowledge, confidence and need for training.

Genetic information is increasingly used in many contexts, including health, insurance, policing and sentencing-with numerous potential benefits and risks. Protecting from the related risks requires updates to laws and procedures by justice systems. These updates depend to a large extent on what the key stakeholders-the judiciary-know and think about the use of genetic information.

Experience from the first UK inter-regional specialist multidisciplinary meeting in the diagnosis and management of IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is a complex multisystem fibro-inflammatory disorder, requiring diagnostic differentiation from malignancy and other immune-mediated conditions, and careful management to minimise glucocorticoid-induced toxicity and prevent progressive organ dysfunction. We describe the experience of the first inter-regional specialist IgG4-RD multidisciplinary team meeting (MDM) incorporating a broad range of generalists and specialists, held 6-weekly via web-link between Oxford University Hospitals NHS Foundation Trust and University College London Hospitals NHS Foundation Trust. Over 3 years, there were 206 discussions on 156 patients.

Limit of detection of troponin discharge strategy versus usual care: randomised controlled trial.

Introduction: The clinical effectiveness of a 'rule-out' acute coronary syndrome (ACS) strategy for emergency department patients with chest pain, incorporating a single undetectable high-sensitivity cardiac troponin (hs-cTn) taken at presentation, together with a non-ischaemic ECG, remains unknown.

Methods: A randomised controlled trial, across eight hospitals in the UK, aimed to establish the clinical effectiveness of an undetectable hs-cTn and ECG (limit of detection and ECG discharge (LoDED)) discharge strategy. Eligible adult patients presented with chest pain; the treating clinician intended to perform investigations to rule out an ACS; the initial ECG was non-ischaemic; and peak symptoms occurred <6 hours previously.

Oxidation of graphene with variable defects: alternately symmetrical escape and self-restructuring of carbon rings.

Variable defects such as vacancies and grain boundaries are unavoidable in the synthesis of graphene, but play a central role in the activation of oxidation. Here, we apply reactive molecular dynamics simulations to reveal the underpinning mechanisms of oxidation in graphene with or without defects at the atomic scale. There exist four oxidation modes generating CO2 or CO in different stages, beginning from a single-atom vacancy, and proceeding until the ordered structure broken down into carbon oxide chains.

Characterization and Immunogenicity of HIV Envelope gp140 Zera Tagged Antigens.

HIV-1 envelope glycoprotein (Env) remains the most relevant target for the elicitation of functional antibodies to HIV by vaccination. However, soluble Env antigens often do not elicit the desired immune responses. Delivering subunit antigens on particulate nanoparticles is an established approach to improve their immunogenicity.

Obeticholic acid-a new therapy in PBC and NASH.

Introduction: Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH).

Sources Of Data: In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase.

Nonlinear time-warping made simple: A step-by-step tutorial on underwater acoustic modal separation with a single hydrophone.

Classical ocean acoustic experiments involve the use of synchronized arrays of sensors. However, the need to cover large areas and/or the use of small robotic platforms has evoked interest in single-hydrophone processing methods for localizing a source or characterizing the propagation environment. One such processing method is "warping," a non-linear, physics-based signal processing tool dedicated to decomposing multipath features of low-frequency transient signals (frequency f < 500 Hz), after their propagation through shallow water (depth D < 200 m) and their reception on a distant single hydrophone (range r > 1 km).

Travel Distance Does Not Affect Outcomes in Hip Preservation Surgery: A Case for Centers of Excellence.

Background: Previous studies have evaluated the effect of distance to high-volume centers on outcomes after joint replacement. However, there is limited evidence on whether this distance has an effect on outcomes after undergoing hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS).

Purpose: To determine whether increased distance from a patient's home to his or her primary orthopaedic clinic has an influence on the ability to achieve the minimal clinically important difference (MCID) on outcome measures after surgery for FAIS.

HIV-exposed infant follow-up in Mozambique: formative research findings for the design of a cluster randomized controlled trial to improve testing and ART initiation.

Background: Early infant diagnosis (EID) of HIV-exposed and initiation of HIV-positive infants on anti-retroviral therapy (ART) requires a well-coordinated cascade of care. Loss-to-follow-up (LTFU) can occur at multiple steps and effective EID is impeded by human resource constraints, difficulty with patient tracking, and long waiting periods. The objective of this research was to conduct formative research to guide the development of an intervention to improve the pediatric HIV care cascade in central Mozambique.

Co-expression of human calreticulin significantly improves the production of HIV gp140 and other viral glycoproteins in plants.

Plant molecular farming (PMF) is rapidly gaining traction as a viable alternative to the currently accepted paradigm of producing biologics. While the platform is potentially cheaper and more scalable than conventional manufacturing systems, expression yields and appropriate post-translational modifications along the plant secretory pathway remain a challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low yields in plants and, in some cases, may not be appropriately processed.

An In Vivo Assessment of Regional Brain Temperature during Whole-Body Cooling for Neonatal Encephalopathy.

Objective: To assess differences in regional brain temperatures during whole-body hypothermia and test the hypothesis that brain temperature profile is nonhomogenous in infants with hypoxic-ischemic encephalopathy.

Study Design: Infants with hypoxic-ischemic encephalopathy were enrolled prospectively in this observational study. Magnetic resonance (MR) spectra of basal ganglia, thalamus, cortical gray matter, and white matter (WM) were acquired during therapeutic hypothermia.

Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis.

Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD.

Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America.

Photoemission from non-polar aromatic molecules in the gas and liquid phase.

The photoelectron spectra of both liquid and gas phase aromatic molecules are reported. The spectra were obtained using a 34.1 eV source produced by high harmonic generation and analysed with the help of high-level ab initio simulations using the reflection principle combined with path integral molecular dynamics simulations accounting for nuclear quantum effects for the gas phase.

Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles.

The HIV-1 envelope glycoprotein (Env) is present on the surface of the virion at a very low density compared to most other enveloped viruses. Substitution of various parts of the stalk domain of Env (gp41) with the corresponding elements from other viral glycoproteins has been shown to increase Env spike density on the cell membrane and surface of virus-like particles (VLPs). In this study, chimeric Env antigens were generated by replacing the transmembrane and cytoplasmic domains of HIV-1 Env with the corresponding regions from the influenza H5 hemagglutinin (HA) (gp140HAtr) and by replacing the entire gp41 region of Env with the HA subunit of HA (gp120HA).

Automation of Controlled/Living Radical Polymerization.

Controlled/living radical polymerization (CLRP) techniques are widely utilized to synthesize advanced and controlled synthetic polymers for chemical and biological applications. While automation has long stood as a high-throughput (HTP) research tool to increase productivity as well as synthetic/analytical reliability and precision, oxygen intolerance of CLRP has limited the widespread adoption of these systems. Recently, however, oxygen-tolerant CLRP techniques, such as oxygen-tolerant photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT), enzyme degassing of RAFT (Enz-RAFT), and atom-transfer radical polymerization (ATRP), have emerged.

Serum ferritin distribution in elite athletes.

Objectives: It is not uncommon for athletes to be diagnosed with iron deficiency, yet there remains uncertainty whether the prevalence of suboptimal iron status in elite athletes differs from the normal population or warrants routine screening. The purpose of this study is to describe the distribution of serum ferritin (SF) in a cohort of elite athletes.

Design: Retrospective cohort study.

The Influence of Lumbosacral Spine Pathology on Minimum 2-Year Outcome After Hip Arthroscopy: A Nested Case-Control Analysis.

Background: Previous literature has examined the association between lumbosacral pathology and hip pathomechanics. However, the effect of lumbosacral pathologies and previous lumbosacral surgery on achieving meaningful outcomes after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) has yet to be studied conclusively.

Purpose: To determine whether a history of lumbosacral spine pathology has an influence on achieving minimal clinically important differences (MCIDs) after hip arthroscopy for FAIS.