Fusing together an outline design for sustained fuelling and tritium self-sufficiency.

Ensuring tritium fuel self-sufficiency while maintaining continuous and high-specification fuel flow to the tokamak via a low tritium inventory and controllable fuel cycle is a significant challenge to the STEP plant design. Effective and high-quality fuelling and exhaust design is required to sustain and control a stable plasma, whereas fuel sufficiency is required to prevent depletion of available tritium supply. Concerns regarding the lack of tritium availability preventing continuous tritium import are countered by breeding, where highly energetic neutrons from the core fusion reactions interact with lithium atoms suspended in the surrounding breeder blanket to produce tritium.

Accurate non-ceruloplasmin bound copper: a new biomarker for the assessment and monitoring of Wilson disease patients using HPLC coupled to ICP-MS/MS.

Objectives: Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed and applied to a cohort of 71 patients, as part of a Wilson Disease Registry Study.

Methods: Elemental copper-protein speciation was developed for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry.

Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator.

Review: Advances in the Accuracy and Traceability of Metalloprotein Measurements Using Isotope Dilution Inductively Coupled Plasma Mass Spectrometry.

Advances in inductively coupled plasma mass spectrometry and the methods used to prepare isotopically enriched standards, allow for the high accuracy measurement of metalloproteins by isotope dilution mass spectrometry. This technique has now reached a level of maturity whereby a step change in the accuracy, precision, and traceability of, in particular, clinical, and biomedical measurements is achievable. Current clinical measurements, which require low limits of detection in the presence of complex sample matrices, use indirect methods based on immunochemistry for the study of human disease.

A Proposed Concept Model for Cancer Risk in Nigerian Electronic Waste Exposure - A Brief Report.

This report aims to render a proposed concept model for cancer risk in Nigerian electronic waste exposure by making deductions from data on the assessment of Nigerians' exposure to toxic metals in e-waste, using biomarkers of exposure and genotoxicity to evaluate the risk of cancer development. In the cross-sectional study, 632 consenting participants, consisting of 381 e-waste workers (EW) and 120 environmental e-waste exposed participants (EEEP), age-matched with 131 unexposed participants (controls), were enrolled from Benin, Lagos and Ibadan, Southwestern Nigeria. Levels of selected toxic metals in blood and essential metals in serum were determined using inductively coupled plasma-mass spectrometry.

Challenges of antithrombotic therapy in the management of cardiovascular disease in patients with inherited bleeding disorders: A single-centre experience.

Introduction: Cardiovascular events in patients with inherited bleeding disorders are challenging to manage. The risk of bleeding secondary to antithrombotic treatment must be balanced against the risk of thrombosis secondary to haemostatic therapy.

Methods: Patients with inherited bleeding disorders with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or atrial fibrillation (AF) from a single centre (2010-2018) are included.

Biomedical copper speciation in relation to Wilson's disease using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry.

Biomedical analytical methods often rely on indirect measurements, such as immunoassays, which can lack effective metrological traceability. In the nephelometric determination of ceruloplasmin (Cp), an important protein whose circulating level is altered in Wilson's disease (WD), the anti-Cp antibody used is not specific for the biologically active holoprotein so the assay can overestimate the concentration of Cp due to the presence of the apoprotein. By providing quantitation using elemental standards, the use of strong anion exchange chromatography (SAX) coupled to triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS-MS) can overcome the drawbacks of methods for the measurement of metalloproteins reliant on immunoassays.

Mediastinal node staging by positron emission tomography-computed tomography and selective endoscopic ultrasound with fine needle aspiration for patients with upper gastrointestinal cancer: Results from a regional centre.

Aim: To investigate the impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and positron emission tomography-computed tomography (PET-CT) in the nodal staging of upper gastrointestinal (GI) cancer in a tertiary referral centre.

Methods: We performed a retrospective review of prospectively recorded data held on all patients with a diagnosis of upper GI cancer made between January 2009 and December 2015. Only those patients who had both a PET-CT and EUS with FNA sampling of a mediastinal node distant from the primary tumour were included.

Measurement of titanium in hip-replacement patients by inductively coupled plasma optical emission spectroscopy.

Background Patients with metal-on-metal hip replacements require testing for cobalt and chromium. There may also be a need to test for titanium, which is used in the construction of the femoral stem in total hip replacements. It is not possible to use quadrupole inductively coupled plasma mass spectrometry due to interferences.

An assessment of clinical laboratory performance for the determination of manganese in blood and urine.

Background: Proficiency testing or external quality assessment schemes (PT/EQASs) are an important method of assessing laboratory performance. As each scheme establishes assigned values and acceptable ranges for the analyte according to its own criteria, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions.

Methods: Standard deviations (SDs) for PT were derived from Thompson's and biological variation models applied to blood and urine manganese (Mn) robust data from four EQASs from North America and Europe.

Radiotherapy and Conservative Surgery in the Locoregional Management of Merkel Cell Carcinoma: The British Columbia Cancer Agency Experience.

Background: Merkel cell carcinoma (MCC) is an uncommon aggressive skin malignancy. Published series mainly focus on wide excision, which can be difficult at some sites (e.g.

Feasibility of asymmetric flow field-flow fractionation coupled to ICP-MS for the characterization of wear metal particles and metalloproteins in biofluids from hip replacement patients.

Hip replacements are used to improve the quality of life of people with orthopaedic conditions, but the use of metal-on-metal (MoM) arthroplasty has led to poor outcomes for some patients. These problems are related to the generation of micro- to nanosized metal wear particles containing Cr, Co or other elements, but the current analytical methods used to investigate the processes involved do not provide sufficient information to understand the size or composition of the wear particles generated in vivo. In this qualitative feasibility study, asymmetric flow field-flow fractionation (AF(4)) coupled with inductively coupled plasma mass spectrometry (ICP-MS) was used to investigate metal protein binding and the size and composition of wear metal particles present in serum and hip aspirates from MoM hip replacement patients.

Analytical approaches to investigating metal-containing drugs.

Many pharmaceuticals contain metals, either as part of the active compound or within the formulation. They are also found in related products such as dietary supplements and toiletries. Concentrations of metals in biological fluids or tissues from patients taking these agents, are measured where there may be an adverse reaction, dose-related toxicity or for therapeutic drug monitoring.

The longest duration of retention of a video capsule.

An underweight 15-year-old boy had a video capsule endoscopy (VCE) to investigate iron deficient anaemia associated with elevated platelet and white cell counts. The suspicion was of subclinical small bowel Crohn's disease after the findings of a radiolabelled white cell scan. The VCE in May 2007 found patchy inflammation and superficial ulcers in the terminal ileum consistent with Crohn's disease.

Outcomes of Merkel cell carcinoma treated with radiotherapy without radical surgical excision.

Background: Achieving clear surgical margins in Merkel cell carcinoma (MCC) can be difficult due to tumor location or patient comorbidity. Clinical impression suggests that radiation treatment achieves good control of macroscopic disease.

Methods: A retrospective chart review was undertaken of all patients with pathological evidence of MCC and treated with curative intent at the BC Cancer Agency between 1979 and 2007.

Removal of the gadolinium interference from the measurement of selenium in human serum by use of collision cell quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS).

Background: Measurement of selenium in serum is an important clinical biomarker of nutritional status. The presence of gadolinium (Gd) in samples following administration of the contrast agents used for magnetic resonance imaging (MRI) results in a significant positive bias when using quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS).

Methods: Three instrumental set-ups were assessed: standard mode with no collision gas and collision cell mode with either a hydrogen:helium mixture or hydrogen.

Metal(loid) levels in biological matrices from human populations exposed to mining contamination--Panasqueira Mine (Portugal).

Mining activities may affect the health of miners and communities living near mining sites, and these health effects may persist even when the mine is abandoned. During mining processes various toxic wastes are produced and released into the surrounding environment, resulting in contamination of air, drinking water, rivers, plants, and soils. In a geochemical sampling campaign undertaken in the Panasqueira Mine area of central Portugal, an anomalous distribution of several metals and arsenic (As) was identified in various environmental media.

Adenovirus-associated virus vector-mediated gene transfer in hemophilia B.

Background: Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder.

Methods: We infused a single dose of a serotype-8-pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values).

Interference of gadolinium on the measurement of selenium in human serum by inductively coupled plasma-quadrupole mass spectrometry.

Selenium is an important clinical biomarker of nutritional status; however, the occurrence of gadolinium in a patient's serum as a result of the contrast agents used during magnetic resonance imaging investigations, results in a significant positive bias in its measurement by inductively coupled plasma-quadrupole mass spectrometry.

Determination of cisplatin 1,2-intrastrand guanine-guanine DNA adducts in human leukocytes by high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry.

Platinum-containing drugs are widely used to treat cancer in a variety of clinical settings. Their mode of action involves the formation of DNA adducts, which facilitate apoptosis in cancer cells. Cisplatin binds to the N7 position of the purine DNA bases forming intrastrand cross-links between either two adjacent guanines [cis-Pt(NH(3))(2)d(pGpG), 1,2-GG] or an adjacent adenine and guanine [cis-Pt(NH(3))(2)d(pApG), 1,2-AG)].

DNA damage in earthworms from highly contaminated soils: assessing resistance to arsenic toxicity by use of the Comet assay.

Earthworms native to the former mine site of Devon Great Consols (DGC), UK reside in soils highly contaminated with arsenic (As). These earthworms are considered to have developed a resistance to As toxicity. The mechanisms underlying this resistance however, remain unclear.

Arsenic biotransformation in earthworms from contaminated soils.

Two species of arsenic (As) resistant earthworm, Lumbricus rubellus and Dendrodrillus rubidus, their host soils and soil excretions (casts) were collected from 23 locations at a former As mine in Devon, UK. Total As concentrations, measured by ICP-MS, ranged from 255 to 13,080 mg kg(-1) in soils, 11 to 877 mg kg(-1) in earthworms and 284 to 4221 mg kg(-1) in earthworm casts from a sub-sample of 10 of the 23 investigated sites. The samples were also measured for As speciation using HPLC-ICP-MS to investigate potential As biotransformation pathways.

Human toenails as a biomarker of exposure to elevated environmental arsenic.

A pilot study was conducted to determine the applicability of toenails as a biomarker of exposure to elevated environmental arsenic (As) levels. A total of 17 individuals were recruited for the pilot study: 8 residents living near to a former As mine, Devon, UK, forming the exposed group, plus 9 residents from Nottinghamshire, UK, with no anticipated As exposure who were used for comparison as a control group. All toenail samples were thoroughly washed prior to analysis and the wash solutions retained for As determination via ICP-MS to provide an indication of the background environmental As levels for each group.