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The electron dynamics of laser wakefield acceleration (LWFA) is examined in the high-density regime using particle-in-cell simulations. These simulations model the electron source as a target of carbon nanotubes. Carbon nanotubes readily allow access to near-critical densities and may have other advantageous properties for potential medical applications of electron acceleration. In the near-critical density regime, electrons are accelerated by the ponderomotive force followed by the electron sheath formation, resulting in a flow of bulk electrons. This behavior represents a qualitatively distinct regime from that of low-density LWFA. A quantitative entropy index for differentiating these regimes is proposed. The dependence of accelerated electron energy on laser amplitude is also examined. For the majority of this study, the laser propagates along the axis of the target of carbon nanotubes in a 1D geometry. After the fundamental high-density physics is established, an alternative, 2D scheme of laser acceleration of electrons using carbon nanotubes is considered.

The dense plasma focus (DPF) can be an intense source of x rays, wherein the insulator sleeve strongly dictates the electrical breakdown, which subsequently affects the formation of a plasma sheath and a collapse phase. Experiments on a 25 kJ DPF (operated at 4.4 kJ) are carried out to demonstrate the influence of insulator surface morphology on the pinch structure, dynamics, and x-ray yield using a Ne fill. Two borosilicate insulators are directly compared, one with a smooth finish and the other machined with four circumferential grooves traversing the perimeter of the exterior insulator surface. Comparisons are made through same-shot imaging diagnostics of the evolving plasma sheath during breakdown, rundown, and at the pinch in addition to the time-resolved measurements of emitted x rays via filtered photodiodes. The presence of structures on the insulator sleeve reduces x-ray production across all fill pressures by a factor of 2.8 ± 2.4 on average and reduces the highest x ray producing shots by a factor of 5.5 ± 1.8. Observations of sheath asymmetry and inhomogeneity at lift-off are observed and correlated with subsequent observations of off-axis radial collapse. Taken together, this suggests that local variations in the insulator surface decrease the spatial uniformity of the sheath, leading to an azimuthally asymmetric focus, reduced electron densities, and, ultimately, degraded x-ray production.

The addition of Kr dopant to a deuterium or deuterium–tritium dense plasma focus (DPF) is conventionally thought to enhance radiative cooling of the imploding sheath, resulting in a tighter pinch and, under optimized conditions, increased neutron yield [M. Krishnan, IEEE Trans. Plasma Sci. 40, 3189 (2012)]. In this work, 2D radiation magnetohydrodynamic (MHD) simulations are conducted of a DPF at peak current levels in the 2–3 MA range with Kr dopant concentrations of 0%, 0.1%, and 1.0% (by volume). Fully kinetic simulations are required to accurately model the pinch stagnation and accurately predict total neutron yield (thermonuclear + beam target), as MHD simulations cannot capture kinetic effects or beam-target neutron production. However, insights can be gained from following the evolution of the bulk dynamics of the sheath. The results show that sheath width narrows with increasing dopant concentration due to increased radiation. Thermonuclear neutron yields of ∼ 10 9 − 10 10 are observed, which is in good agreement with experimental data [E. N. Hahn et al., J. Appl. Phys. 128, 143302 (2020)] and simulations [N. Bennett et al., Phys. Plasmas 24, 021702 (2017)] that measure yields of ∼ 10 11 at ∼ 2 MA with ∼ 1% of that yield having thermonuclear origin. Scaling in excess of the conventional ∝ I 4 scaling is observed, though this should be confirmed with 3D and/or fully kinetic simulations of Kr-doped DPFs.

Experiments on a MA-class Dense Plasma Focus (DPF) device have been carried out to investigate changes in neutron production by adding moderate amounts of krypton to a deuterium fill gas. The neutron yield from Z-pinch devices, including DPFs, conventionally scales as the peak current to the fourth power. However, a dramatic drop-off from ∼I4 scaling occurs above 3 MA, which recent modeling [D. T. Offermann et al., Phys. Rev. Lett. 116, 195001 (2016)] attributed to the transition in the predominant neutron production mechanism from beam-target fusion to thermonuclear fusion. Previously, the addition of Kr (and other high-Z) dopants has been shown to enhance beam-target fusion yields at currents below 300 kA, with optimal concentrations at 1%–2% Kr, whereas here we show that the optimal concentration of Kr at the MA level is near 0.1% by volume—elucidating a trend in the optimal Kr doping concentration as a function of the device scale. The neutron time-of-flight data reveal that Kr doping creates shorter and more intense neutron bursts, likely due a tighter but unstable pinch, highlighting a key trade-off for Kr doping.

There is a wide variation in laboratory practice with regard to implementation and review of internal quality control (IQC). A poor approach can lead to a spectrum of scenarios from validation of incorrect patient results to over investigation of falsely rejected analytical runs. This article will provide a practical approach for the routine clinical biochemistry laboratory to introduce an efficient quality control system that will optimise error detection and reduce the rate of false rejection. Each stage of the IQC system is considered, from selection of IQC material to selection of IQC rules, and finally the appropriate action to follow when a rejection signal has been obtained. The main objective of IQC is to ensure day-to-day consistency of an analytical process and thus help to determine whether patient results are reliable enough to be released. The required quality and assay performance varies between analytes as does the definition of a clinically significant error. Unfortunately many laboratories currently decide what is clinically significant at the troubleshooting stage. Assay-specific IQC systems will reduce the number of inappropriate sample-run rejections compared with the blanket use of one IQC rule. In practice, only three or four different IQC rules are required for the whole of the routine biochemistry repertoire as assays are assigned into groups based on performance. The tools to categorise performance and assign IQC rules based on that performance are presented. Although significant investment of time and education is required prior to implementation, laboratories have shown that such systems achieve considerable reductions in cost and labour.

Background. Biomarkers to distinguish latent from activeMycobacterium (M.) tuberculosisinfection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients withM. tuberculosisinfection.Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latentM. tuberculosisinfection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated.Results. We included a total of 44 patients withM. tuberculosisinfection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latentM. tuberculosisinfection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p<0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p<0.01).Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients withM. tuberculosisinfection.

Background Internal quality control (IQC) has a long and well-established role in clinical biochemistry laboratories. However, despite the duration of use, and the publication of several articles detailing best practice, the implementation and use of IQC vary significantly between institutions. Consequently, the North Thames Audit and Quality Assurance Group undertook a region-wide audit of current IQC practice in 2006. Methods On aspects of IQC testing, interpretation and laboratory processes, 54 laboratories in the region were audited. Results Audit data showed significant variability in all aspects of practice, including IQC frequency, use of appropriate material, statistical processing and grades of staff involved. Conclusions Some of the variation in practice may affect the effectiveness of laboratory IQC, and thus the adequacy of a laboratory to monitor system performance. Consequently, a set of proposed regional standards have been developed and disseminated, prior to re-audit at a future date.

The Soufrière Hills stratovolcano on the Caribbean island of Montserrat has been erupting since 18th July 1995. An enormous amount of respirable volcanic ash has been suspended into the atmosphere by the eruptions and wind re-suspension of deposited ash. The large amount of fine, airborne particulate matter, in particular the component 10 μm equivalent aerodynamic diameter (PM10), is a cause of medical concern. Airborne levels have frequently exceeded the UK environmental standard for PM10, (50 μg/m3), although it is noted that this standard was primarily set for urban PM10. The crystalline silica in the ash is mostly cristobalite, at reported levels up to 20%. The UK government’s Chief Medical Officer, referring to Montserrat, has suggested that long-term exposure to high levels of volcanic ash could lead to silicosis. These concerns have prompted government-funded investigations into the potential toxicity of well characterized volcanic ash samples from Montserrat. Given the well established toxicity of cristobalite, particular attention was paid to the amount of this mineral in the ash samples. Three ash samples were tested: (1) a vulcanian eruption ash, (2) ash released in a domecollapse pyroclastic flow, and (3) ash from a major vulcanian explosion that was wind-transported to, and deposited on, the neighbouring island of Antigua. Comparative toxicological studies were carried out on respirable preparations of these three samples together with appropriate control mineral dusts that matched the major components of the Montserrat samples: anorthite, labradorite, cristobalite/ obsidian and cristobalite. Alpha quartz (DQ12) was the positive control. All samples, including the controls, were characterized to establish particle-size distributions, particle morphologies, and to confirm the mineralogy. Rats were challenged with 1 mg via intratracheal instillation, and groups sacrificed at three time points (1, 3 and 9 weeks). Health assessment was made by examining endpoints of increasing lung damage such as inflammation, permeability (oedema), changes in epithelium, and increase in the size of broncho-thoracic lymph nodes. The data indicate that Montserrat respirable ash, derived from dome collapse pyroclastic flows or vulcanian explosions, has minimal acute bioreactivity in the lung. The feldspar standards showed low bioreactivity, in stark contrast to the cristobalite standard that showed progressive increases in lung damage. These results suggest that either the mass of cristobalite present in the Montserrat ash was insufficient to cause an effect in the lung, or the cristobalite in the ash was, for some as yet unknown reason, markedly less bioreactive than our pure cristobalite standard.

Hyperammonaemia causing encephalopathy and coma is a recognized but rare cause of altered mental status in patients with urinary diversions, most commonly associated with ureterosigmoidostomy although also with ileal conduits. We describe the case of a 41-year-old lady with an ileal conduit who developed severe hyperchloraemic metabolic acidosis and associated hyperammonaemia. This led to a significant decrease in her Glasgow Coma Score such that she required Intensive Therapy Unit management. We review the current literature on this condition, discussing its aetiology and management.

The term Munchausen syndrome is used to describe the patient who chronically fabricates or induces illness with the sole intention of assuming the patient role. Such persons often have a close association with the medical profession and thus use their knowledge to falsify symptoms and laboratory specimens to mimic disease. Cases of factitious disease have appeared in the literature originating from all medical specialties, and include such rare disorders as phaeochromocytoma and Bartter's syndrome. The laboratory can play a key role in the detection and diagnosis of factitious disorders. Indeed discrepant biochemistry results may provide the first clue to the diagnosis. Laboratory staff should be particularly aware of highly variable test results and extreme abnormalities that are not consistent with the wider biochemical profile, suggesting sample tampering. Factitious disorder should also be included in the clinician's differential diagnosis when disease presentation is unusual or an underlying cause cannot be found. Investigation to exclude or confirm factitious disorder at an early stage can prevent unnecessary testing in the search for increasingly rare diseases. Appropriate analyses may include screening tests for the detection of surreptitious drug administration or replication of a fabricated sample to confirm the method used. In all cases close communication between the clinician and laboratory is essential. This will ensure that appropriate tests are conducted particularly with regard to time critical and repeat tests.

The entire respiratory tract is continually exposed to a variety of oxidants, of which a large percentage may react within the nasal passages. In the secretions lining the human nasal cavity uric acid has been shown to be the only low molecular weight antioxidant present in abundance. Because this uric acid originates in the plasma, it is possible that factors affecting the levels of plasma uric acid will also alter the levels recovered in lavage fluids. Lavage fluid from 15 men (20-68 years) and 11 women (20-59 years) were collected using a modified Foley catheter which allowed each subject to supply a basal lavage (saline removed immediately after instillation) and an "accrued' lavage (saline left in situ for 5 min) from each nasal cavity. Lavage fluids were assayed for protein, lysozyme and uric acid. The levels of protein and lysozyme in the recovered fluids were found not to be affected by subject age or gender. Uric acid, however, was found to have a weak negative (r2 = -0.685 basal and -0.62 accrued) correlation with age in women, but no such correlation was noted in men. Also, the levels of uric acid in women (1.3 +/- 0.3 microM/L basal and 4.5 +/- 0.6 microM/L accrued) were found to be lower than those seen in men (3.1 +/- 0.6 microM/L basal and 8.4 +/- 1.3 microM/L accrued) (p = 0.0681 and 0.0394 respectively). It is concluded that women have lower levels of uric acid in lavage fluids than men, with subject age also possibly affecting lavage uric acid. It is also proposed that such factors which lead to decreased levels of uric acid may be related to individual sensitivity to inhaled oxidants such as ozone.

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependent manner.

Profound hypocalcaemia is an uncommon presentation from primary care. We describe a case of hypocalcaemia presenting 4 years after total thyroidectomy. Long-term complications of chronic hypocalcaemia are rarely seen in clinical practice today, but had occurred in this case with the development of bilateral cataracts. All patients should be monitored following thyroidectomy to ensure that hypocalcaemia does not persist. In addition to this, patients with a history of thyroid surgery presenting with cataracts should have serum calcium measured.

Several factors predisposing patients to statin-induced myopathy have been described. We describe a patient whose statin intolerance was associated with changes in serum potassium arising from previously undiagnosed Gitelman's syndrome.

Background: The Soufriere Hills, a stratovolcano on Montserrat, started erupting in July 1995, producing volcanic ash, both from dome collapse pyroclastic flows and phreatic explosions. The eruptions/ash resuspension result in high concentrations of suspended particulate matter in the atmosphere, which includes cristobalite, a mineral implicated in respiratory disorders. Aims: To conduct toxicological studies on characterised samples of ash, together with major components of the dust mixture (anorthite, cristobalite), and a bioreactive mineral control (DQ12 quartz). Methods: Rats were challenged with a single mass (1 mg) dose of particles via intratracheal instillation and groups sacrificed at one, three, and nine weeks. Acute bioreactivity of the particles was assessed by increases in lung permeability and inflammation, changes in epithelial cell markers, and increase in the size of bronchothoracic lymph nodes. Results: Data indicated that respirable ash derived from pyroclastic flows (20.1% cristobalite) or phreatic explosion (8.6% cristobalite) had minimal bioreactivity in the lung. Anorthite showed low bioreactivity, in contrast to pure cristobalite, which showed progressive increases in lung damage. Conclusion: Results suggests that either the percentage mass of cristobalite particles present in Montserrat ash was not sufficient as a catalyst in the lung environment, or its surface reactivity was masked by the non-reactive volcanic glass components during the process of ash formation.

A method has been developed that uses chemiluminescent acridinium esters rather than radioactive iodine in an immunoassay for albumin. Albumin is a protein derived from plasma sources found in nasal fluids. As such, it can be used as an important marker of plasma exudation in experimental rhinology. The assay was developed as an alternative to radioimmunoassay for a number of reasons: chemiluminescent assays do not require radioactive materials and the complex safety related aspects of their usage; the assays are easy to perform and do not require expensive equipment; and the assay is capable of the sensitivity required to detect very small changes in albumin concentrations in nasal fluids. The assay measures albumin with a sensitivity of 1.2 ng/ml. The working range of the assay is 1.0-23.7 micrograms/ml with an interassay coefficient of variation < or = 15%. This working range encompasses the range of albumin usually found in nasal lavage samples from normal volunteers.

Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic control. It is considered important in nasal defence as it enzymatically hydrolyses peptidoglycan bonds in bacterial cell walls and has specific activity against Gram-positive bacteria in vitro. Oxymetazoline is freely available as a non-prescription nasal decongestant. Some recent work has shown that it has no effect on histamine-induced plasma exudation but little is known about its effects on glandular secretion. The current study is a randomized controlled study that investigates the effect of topical oxymetazoline on the total protein and lysozyme content of nasal fluid. Thirty healthy volunteers were randomized to receive either a normal saline nasal spray (placebo) or an active spray of oxymetazoline, 0.05% (w/v) in saline. NAR was assessed in all subjects using posterior rhinomanometry and nasal lavage before the application of the spray and again 10 min later. The results were analysed using non-parametric statistics. There was a significant decrease in both the lysozyme and total protein content of nasal lavage after application of oxymetazoline when compared with placebo (p < 0.05). A possible mechanism for the observed decease in total protein and lysozyme would be that the vasoconstrictor effects of oxymetazoline also apply to the vessels supplying nasal submucosal glands and that this decrease in blood supply is reflected by a decrease in secretion.

The toxicity of ozone, the major component of photochemical smog, is related to its powerful oxidising ability, and many of its deleterious effects are mediated through free radical reactions. As the majority of ozone oxidation events are thought to be confined to the pulmonary epithelial lining fluid, we studied the interaction of ozone with a range of small molecular weight antioxidants found within this compartment: ascorbic acid (AH2), uric acid (UA), and reduced glutathione (GSH). Epithelial lining fluid obtained as bronchoalveolar lavage (BAL) fluid, was taken from 16 male subjects and the antioxidant concentrations determined for each subject. BAL fluid samples from nine of these subjects were then exposed, using an interfacial exposure system, to a range (50-1000 ppb) of ozone concentrations. Both AH2 and UA were consumed by ozone in a time and ozone concentration dependent manner, with mean consumption rates of 1.7 +/- 0.8 and 1.0 +/- 0.5 pmol L-1 s-1 ppb-1, respectively. Considerable intersubject variation was however observed. The individual rates of consumption for each antioxidant were significantly correlated with the respective initial antioxidant concentration. In contrast, although GSH was consumed at 50 ppb ozone, the rate of consumption did not change with increasing ozone concentration. We conclude that there is differential depletion of BAL fluid antioxidants, suggesting a reactivity hierarchy toward ozone in human ELF of AH2UAGSH.