The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: a consensus guideline.

This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.

Brainstem cavernous malformations - no longer a forbidden territory? A systemic review of recent literature.

BACKGROUND: Due to its eloquent location and potentially devastating neurological consequences, the management of brainstem cavernous malformations (CCMs) attracts considerable debate. There is currently a paucity of Level 1 evidence for their management. The aim of this literature review is to explore the current evidence on the risk-benefit profile of different management options. METHODS: A systemic literature search, following the PRISMA algorithm was performed on publications between 2010 and 2018 using the Pubmed database, with the relevant keywords. Only English articles were included. Articles focusing on spinal CCMs and studies with less than 30 participants were excluded. RESULTS: A total of 222 search results were reviewed and after removal of duplicates and screening of abstracts, 28 clinical papers comprising 30 or more brainstem CCM cases were included in the study. The heterogeneity of the publications precluded a formal meta-analysis of results. The general consensus is that for CCMs presenting with severe symptoms and/or multiple haemorrhages that reach an accessible pial surface, surgery is considered to be the gold-standard treatment, with some authors suggesting the optimal timing to be within two to six weeks of ictus. For those patients with multiple, deep-seated CCM related haemorrhages that do not reach the pial surface, stereotactic radiosurgery (SRS) can be considered. Conservative treatment is generally considered in incidental cases. Management of brainstem cavernomas of other categories still remains controversial. CONCLUSIONS: Due to their highly eloquent location, brainstem CCMs are challenging lesions to manage. Management must be balanced by the risk-benefit profile and tailored to the individual patients and their treating clinicians. This review provides a comprehensive reference considering all treatment options and provides a basis for evidence-based patient counselling.

Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE-/- mouse model of atherosclerosis with alterations in IL10/AMPKα pathway.

OBJECTIVE: Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD. METHODS: We generated novel macrophage-specific PTP1B knockout mice on atherogenic background (ApoE-/-/LysM-PTP1B). Mice were fed standard or pro-atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis, atherosclerotic plaque development, and molecular, biochemical and targeted lipidomic eicosanoid analyses were performed. RESULTS: Myeloid-PTP1B knockout mice on atherogenic background (ApoE-/-/LysM-PTP1B) exhibited a striking improvement in glucose homeostasis, decreased circulating lipids and decreased atherosclerotic plaque lesions, in the absence of body weight/adiposity differences. This was associated with enhanced phosphorylation of aortic Akt, AMPKα and increased secretion of circulating anti-inflammatory cytokine interleukin-10 (IL-10) and prostaglandin E2 (PGE2), without measurable alterations in IR phosphorylation, suggesting a direct beneficial effect of myeloid-PTP1B targeting. CONCLUSIONS: Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE-/- mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

Controlling superstructural ordering in the clathrate-I Ba8M16P30 (M = Cu, Zn) through the formation of metal-metal bonds.

Order-disorder-order phase transitions in the clathrate-I Ba8Cu16P30 were induced and controlled by aliovalent substitutions of Zn into the framework. Unaltered Ba8Cu16P30 crystallizes in an ordered orthorhombic (Pbcn) clathrate-I superstructure that maintains complete segregation of metal and phosphorus atoms over 23 different crystallographic positions in the clathrate framework. The driving force for the formation of this Pbcn superstructure is the avoidance of Cu-Cu bonds. This superstructure is preserved upon aliovalent substitution of Zn for Cu in Ba8Cu16-x Zn x P30 with 0 < x < 1.6 (10% Zn/Mtotal), but vanishes at greater substitution concentrations. Higher Zn concentrations (up to 35% Zn/Mtotal) resulted in the additional substitution of Zn for P in Ba8M16+y P30-y (M = Cu, Zn) with 0 ≤ y ≤ 1. This causes the formation of Cu-Zn bonds in the framework, leading to a collapse of the orthorhombic superstructure into the more common cubic subcell of clathrate-I (Pm3n). In the resulting cubic phases, each clathrate framework position is jointly occupied by three different elements: Cu, Zn, and P. Detailed structural characterization of the Ba-Cu-Zn-P clathrates-I via single crystal X-ray diffraction, joint synchrotron X-ray and neutron powder diffractions, pair distribution function analysis, electron diffraction and high-resolution electron microscopy, along with elemental analysis, indicates that local ordering is present in the cubic clathrate framework, suggesting the evolution of Cu-Zn bonds. For the compounds with the highest Zn content, a disorder-order transformation is detected due to the formation of another superstructure with trigonal symmetry and Cu-Zn bonds in the clathrate-I framework. It is shown that small changes in the composition, synthesis, and crystal structure have significant impacts on the structural and transport properties of Zn-substituted Ba8Cu16P30.

Structures, Phase Transitions and Tricritical Behavior of the Hybrid Perovskite Methyl Ammonium Lead Iodide.

We have examined the crystal structures and structural phase transitions of the deuterated, partially deuterated and hydrogenous organic-inorganic hybrid perovskite methyl ammonium lead iodide (MAPbI3) using time-of-flight neutron and synchrotron X-ray powder diffraction. Near 330 K the high temperature cubic phases transformed to a body-centered tetragonal phase. The variation of the order parameter Q for this transition scaled with temperature T as Q ∼ (Tc-T)ß, where Tc is the critical temperature and the exponent ß was close to », as predicted for a tricritical phase transition. However, we also observed coexistence of the cubic and tetragonal phases over a range of temperature in all cases, demonstrating that the phase transition was in fact first-order, although still very close to tricritical. Upon cooling further, all the tetragonal phases transformed into a low temperature orthorhombic phase around 160 K, again via a first-order phase transition. Based upon these results, we discuss the impact of the structural phase transitions upon photovoltaic performance of MAPbI3 based solar cells.

Anisotropic Exchange within Decoupled Tetrahedra in the Quantum Breathing Pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11}.

The low energy spin excitation spectrum of the breathing pyrochlore Ba_{3}Yb_{2}Zn_{5}O_{11} has been investigated with inelastic neutron scattering. Several nearly resolution limited modes with no observable dispersion are observed at 250 mK while, at elevated temperatures, transitions between excited levels become visible. To gain deeper insight, a theoretical model of isolated Yb^{3+} tetrahedra parametrized by four anisotropic exchange constants is constructed. The model reproduces the inelastic neutron scattering data, specific heat, and magnetic susceptibility with high fidelity. The fitted exchange parameters reveal a Heisenberg antiferromagnet with a very large Dzyaloshinskii-Moriya interaction. Using this model, we predict the appearance of an unusual octupolar paramagnet at low temperatures and speculate on the development of intertetrahedron correlations.

Defining the impact of individual sample variability on routine immunoassay of serum free light chains (sFLC) in multiple myeloma.

Serum free light chain (sFLC) measurement has gained widespread acceptance and is incorporated into various diagnostic and response criteria. Non-linearity and antigen excess are the main causes of 'variability' in the measurement of sFLC using immunoassay, but the impact of these on measurement has been unclear. We performed a retrospective evaluation using a dilutional strategy to detect these phenomena. A total of 464 samples in 2009 and 373 samples in 2010 were analysed for sFLC. Non-linearity was detected in both high and apparently normal sFLC. Major non-linearity of more than twofold is common in high kappa (20·2%) and lambda (14·1%). It is less common in samples with apparently normal levels - kappa (6·4%) and lambda (9·5%). 9·4% of kappa and 15·5% of lambda showed antigen excess at screening dilutions. 34·4% of the samples had either non-linearity or antigen excess. We conclude that significant measurement variability is common in the measurement of sFLC. There is currently no reliable technique to detect non-linearity phenomena unless a serial dilution strategy is applied to every analysis. We recommend that laboratories routinely reporting sFLC results for clinical services need appropriate strategies for addressing these issues. Clinicians should be aware of these limitations in interpretation of sFLC assay for individual patients. Future guidelines should adopt action thresholds which are grounded firmly in test performance parameters.

An association between cerebral aneurysm re-bleed and CT angiography--more than a coincidence?

Rupture of cerebral aneurysm during CT angiogram is a rare occurrence. Here we present such a case where an aneurysmal re-rupture during CT angiogram was demonstrated.

Anatomical and surgical considerations of the external branch of the superior laryngeal nerve: a systematic review.

The anatomical course of the external branch of the superior laryngeal nerve (EBSLN) is variable, and a consistent approach to its preservation during thyroid surgery is needed to reduce risk of post-operative voice impairment. Despite agreement that careful dissection in the region of the superior thyroid pole is required, there is no accepted 'best' approach, nor any universal acknowledgement that location of the EBSLN is actually necessary. The popular cernea classification of EBSLN has limitations, including its decreased reliability with increased thyroid size and its irrelevance in cases of 'buried' variants. * Recent work has identified factors such as ethnicity and stature in the prevalence of EBSLN variants. Consistent approaches to the post-operative detection of EBSLN injury are needed to build an accurate picture of the incidence of surgical nerve injury. Then a standardised approach to EBSLN preservation may emerge.

Monitoring enzyme replacement therapy in Fabry disease--role of urine globotriaosylceramide.

Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme. Enzyme replacement therapy (ERT) offers a specific treatment for patients with Fabry disease, though monitoring of treatment is hampered by a lack of surrogate markers of response. In this study, the efficacy of long-term ERT in six Fabry hemizygotes and two symptomatic heterozygotes has been evaluated. Patients were administered recombinant alpha-galactosidase A every 2 weeks for up to a year. The efficacy of ERT was assessed by monitoring symptomatology and renal function. Urinary glycolipid concentration was estimated by a novel tandem mass spectrometric method. Urine glycolipid (Gb(3)) was elevated at baseline and fell impressively on ERT where patients were hemizygotes and in the absence of renal transplantation. In heterozygotes and in a recipient of a renal allograft, elevations and changes in urine glycolipids were less pronounced. In one patient, after several months of ERT, there was a transient increase in Gb(3) concentrations to baseline (pre-ERT) levels, associated with the presence of antibodies to the recombinant alpha-galactosidase A. The marked decline in urine Gb(3) on ERT, and its subsequent increase in association with an inhibitory antibody response, suggest that this analyte deserves further investigation as a potential marker of disease severity and response to treatment.

Intestinal helminth parasites in flounder Platichthys flesus from the River Thames: an infracommunity analysis.

An analysis was undertaken of intestinal helminth communities in flounder Platichthys flesus from two sites on the River Thames. A comparison was made between helminth community richness and diversity from these sites at the component and infracommunity levels. At the component community level, a richer and more diverse parasite community was found in flounder from the Tilbury location (marine influence) than that from the Lots Road location (freshwater influence). At the infracommunity level, more parasite species and parasite individuals per host were found at Lots Road and the percentage of similarity values were low at both locations. Helminth species with high prevalence values in the parasite communities of the flounder are the dominant species in any individual fish, harbouring multi-specific infections. The presence of more invertebrate species, which are intermediate hosts in the helminth life cycle in the Thames, fish vagility and the high prevalence and abundance values of Pomphorhynchus laevis in the flounder, may explain the differences between the two locations.

A comparison of topical formulations for the prevention of human schistosomiasis.

Recently, a dimeticone formulation has been shown to be effective at preventing Schistosoma cercariae infecting skin, while DEET (N,N-diethyl-m-toluamide), a highly effective insecticide, has been shown to have activity against cercariae. Seven formulations, 3 containing DEET, were prepared and applied to excised human skin in Franz cells for 1 h. Schistosoma cercariae were applied for 30 min at 1 and 24 h, and the number that penetrated the skin calculated (n = 9). DEET could not be incorporated into the dimeticone formulation, yet it remained the most effective at preventing cercarial penetration, both 1 and 24 h after application. The ointments that contained DEET did prevent penetration but their mode of action was due to the toxicity of DEET against the cercariae. The persistence of the protection afforded by the dimeticone formulation after washing suggests that the formulation may be interacting with the stratum corneum to prevent cercarial recognition of skin.

Pallisentis rexus from the Chiang Mai Basin, Thailand: ultrastructural studies on egg envelope development and the mechanism of egg expansion.

Pallisentis rexus Wongkham & Whitfield, 1999 (Eoacanthocephala: Quadrigyridae) infects the freshwater snakehead fish, Channa striata, in the Chiang Mai Basin, Thailand. All stages of egg development within the body cavity of the female parasite were observed, using transmission electron microscopy. Changes in mature eggs after contact with water were also investigated. The mature egg has five egg envelopes separated from each other by four gaps. The fertilization membrane, which is formed first, is pushed centrifugally by other, subsequently formed, envelopes and gaps, which produces a final total shell thickness of 8-36 microm around the acanthor. The disappearance of the outermost layer and the unpleating of an adjacent inner layer causes the expansion of eggs on contact with water. The volume of an expanded egg is approximately 27 times that of an unexpanded one, but the density of eggs is reduced from a value greater than water to one almost equal to water. This is believed to aid the dispersion of eggs.

Metastatic adenocarcinoma masquerading as a solitary nerve sheath tumour.

We present a case of a solitary metastasis of an adenocarcinoma to a dorsal root ganglion (DRG) following a disease free interval of 12 years after resection of a Duke's C carcinoma. The presentation of this unusually placed metastasis was associated with a 3-year complex pain syndrome and radiological appearances consistent with benign disease. The case highlights the importance of not dismissing unusual lesions as innocent in the presence of a history of malignant disease.