A comparison of odor plume-tracking behavior of walking and flying insects in different turbulent environments.

Many animals locate food, mates and territories by following plumes of attractive odors. There are clear differences in the structure of this plume-tracking behavior depending on whether an animal is flying, swimming, walking or crawling. These differences could arise from different control rules used by the central nervous system during these different modes of locomotion or one set of rules interacting with the different environments while walking on the surface versus flying or swimming. Flow speeds and turbulence that characterize the environments where walking and flying insects track plumes may alter the structure of odor plumes in an environment-specific way that results in the same control rules generating behaviors that appear quite different. We tested these ideas by challenging walking male cockroaches, Periplaneta americana, and flying male moths, Manduca sexta, to track plumes of their species' sex pheromones in low wind speeds characteristic of cockroach experimental environments, higher wind speeds characteristic of moth experimental environments, and conditions ranging from low to high turbulence. Introducing a turbulence-generating structure into the flow significantly improved the flying plume tracker's ability to locate the odor source, and changed the structure of the behavior of both flying and walking plume trackers. Our results support the idea that plume trackers moving slowly along the substrate may use the spatial distribution of odor, while faster moving flying plume trackers may use the timing of odor encounters to steer to locate the source.

Radiological follow-up of endovascularly treated intracranial aneurysms: a survey of current practice in the UK and Ireland.

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.

A survey of the radiological follow-up of unruptured intracranial aneurysms in the United Kingdom.

OBJECTIVE: Unruptured intracranial aneurysms (UIA) are common. For many the treatment risks outweigh their risk of subarachnoid haemorrhage and patients undergo surveillance imaging. There is little data to inform if and how to monitor UIAs resulting in widely varying practices. This study aimed to determine the current practice of unruptured UIA surveillance in the United Kingdom. METHODS: A questionnaire was designed to address the themes of surveillance protocols for UIA including when surveillance is initiated, how frequently it is performed, and when it is terminated. Additionally, how aneurysm growth is managed and how clinically meaningful growth is defined were explored. The questionnaire was distributed to members of the British Neurovascular Group using probability-based cluster and non-probability purposive sampling methods. RESULTS: Responses were received from 30 of the 30 (100.0%) adult neurosurgical units in the United Kingdom of which 27 (90.0%) routinely perform surveillance for aneurysm growth. Only four units had a unit policy. The mean patient age up to which a unit would initiate follow-up of a low-risk UIA was 65.4 ± 9.0 years. The time points at which imaging is performed varied widely. There was an even split between whether units use a fixed duration of follow-up or an age threshold for terminating surveillance. Forty percent of units will follow-up patients more than 5 years from diagnosis. The magnitude in the change in size that was felt to constitute growth ranged from 1 to 3mm. No units routinely used vessel wall imaging although 27 had access to 3T MRI capable of performing it. CONCLUSIONS: There is marked heterogeneity in surveillance practices between units in the United Kingdom. This study will help units better understand their practice relative to their peers and provide a framework forplanning further research on aneurysm growth.

Linkage to care after HIV diagnosis among men who have sex with men and transgender women in Lima, Peru.

In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage within 90 days of HIV diagnosis by matching data from two studies conducted in Lima between 2013 and 2015 to national ART program records. We used generalized linear modeling to assess predictors of timely linkage and late presentation to care. Of 487 newly-diagnosed MSM and TW, only 44% presented for care at an HIV clinic within 90 days. Timely linkage was less common among TW (aPR 0.7, 95% CI 0.5-1.0), those younger than 24 (aPR 0.8, 95% CI 0.6-1.0), and those reporting a history of sex work (aPR 0.7, 95% CI 0.6-0.9). Proximity to an ART program clinic was not associated with linkage; most participants linked to clinics offering "LGBTQ-friendly" care. The pattern of clinics selected by participants suggests the importance of concerns about confidentiality and stigma in decision-making about where to link to care.

Obstructive hydrocephalus secondary to a perianeurysmal cyst: a case report.

Perianeurysmal cysts are an extremely rare association with cerebral aneurysms. We report the case of a 64 year old male who presented with obstructive hydrocephalus due to a perianeurysmal cyst. The cyst originated in association with a thrombosed, right-sided, terminal internal carotid artery aneurysm. Definitive management was offered with craniotomy and surgical clipping of the aneurysm together with endoscopic cyst fenestration. The patient made a full recovery and was asymptomatic at 3-month follow-up. We review the literature and discuss the potential mechanisms of cyst formation.

Development of the Melanoma Concerns Questionnaire (MCQ-28); refinement of the EORTC QLQ-MEL38 module.

OBJECTIVE: Few patient-reported outcome measures (PROMs) have been developed that adequately measure the patient-experience following diagnosis and treatment of melanoma. Building on previous research, which developed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Module (QLQ-MEL38), the aim of this study was to further test the hypothesised domain structure and psychometric properties of the phase 3 module, in a new larger sample of melanoma patients. METHODS: Melanoma patients (n = 270) were recruited from four countries (Australia, England, Serbia, and Spain). Patients completed the EORTC core questionnaire (QLQ-C30), the QLQ-MEL38, and a sociodemographic survey. Using this new larger dataset, comparisons were made with the hypothesised domain structure of the EORTC phase 3 module using principal component analysis. Items which formed subscales in a revised domain structure were then tested for goodness of fit (GoF) to the Rasch model. RESULTS: The original hypothesised and final domain structures were similar but not identical. Twenty-four items (83%) loaded onto the same distinct subscales previously generated by phase 3, and item-by-item comparison of the two pattern matrices indicated an extremely close match. Ten items were removed from the QLQ-MEL38 phase 3 module, and rescoring of some items was required. Four subscales, together with five individual items, comprised the final instrument. CONCLUSION: The newly developed measure (named the Melanoma Concerns Questionnaire; MCQ-28) was found to tap into several important psychosocial domains of concern to melanoma patients, particularly those being managed in "usual" clinic settings.

Characterizing Men Who Have Sex with Transgender Women in Lima, Peru: Sexual Behavior and Partnership Profiles.

HIV prevalence is high among transgender women (TW), but how HIV is transmitted to this population is not well understood. This analysis aims to characterize sexual partners of TW (PTW) to understand how their behavior contributes to HIV risk among TW. We examined baseline data from TW, PTW, and men who have sex with men (MSM) from a treatment-as-prevention study in Lima, Peru. Individual and partnership characteristics were compared across groups, and Poisson regression was used to calculate prevalence ratios for associations between sexual concurrency and potential correlates. We found that 81% of PTW had no cisgender male partners. Prevalence of alcohol dependency, concurrency, and condomless anal intercourse was high and HIV testing was low compared to the other groups. Our results suggest that PTW are a distinct population from MSM and TW, engage in behavior associated with HIV transmission, and are likely not well reached by HIV prevention interventions.

Three-dimensional imaging of dislocations in a nanoparticle at atomic resolution.

Dislocations and their interactions strongly influence many material properties, ranging from the strength of metals and alloys to the efficiency of light-emitting diodes and laser diodes. Several experimental methods can be used to visualize dislocations. Transmission electron microscopy (TEM) has long been used to image dislocations in materials, and high-resolution electron microscopy can reveal dislocation core structures in high detail, particularly in annular dark-field mode. A TEM image, however, represents a two-dimensional projection of a three-dimensional (3D) object (although stereo TEM provides limited information about 3D dislocations). X-ray topography can image dislocations in three dimensions, but with reduced resolution. Using weak-beam dark-field TEM and scanning TEM, electron tomography has been used to image 3D dislocations at a resolution of about five nanometres (refs 15, 16). Atom probe tomography can offer higher-resolution 3D characterization of dislocations, but requires needle-shaped samples and can detect only about 60 per cent of the atoms in a sample. Here we report 3D imaging of dislocations in materials at atomic resolution by electron tomography. By applying 3D Fourier filtering together with equal-slope tomographic reconstruction, we observe nearly all the atoms in a multiply twinned platinum nanoparticle. We observed atomic steps at 3D twin boundaries and imaged the 3D core structure of edge and screw dislocations at atomic resolution. These dislocations and the atomic steps at the twin boundaries, which appear to be stress-relief mechanisms, are not visible in conventional two-dimensional projections. The ability to image 3D disordered structures such as dislocations at atomic resolution is expected to find applications in materials science, nanoscience, solid-state physics and chemistry.

Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Background: Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance. Methods: In a cross-sectional study (n = 130) we investigated 70 male non-diabetic CKD patients (21 CKD stage 2-3a, 27 CKD stage 3b-4 and 22 CKD stage 5) employing specialized cardiopulmonary exercise testing to measure peak cardiac output and cardiac power output non-invasively. Data from 35 age-matched healthy male volunteers were obtained for comparison. In addition, as a positive control, data from 25 age-matched male HF patients in New York Heart Association class II and III were also obtained. Results: The study subjects showed a graded reduction in peak cardiac power, with 6.13 ± 1.11 W in controls, 5.02 ± 0.78 W in CKD 2-3a, 4.59 ± 0.53 W in CKD 3b-4 and 4.02 ± 0.73 W in CKD 5, although not as impaired as in HF, with 2.34 ± 0.63 W (all P < 0.005 versus control). The central haemodynamic characteristics of the cardiac impairment in CKD mirrored that of HF, with reduced flow and pressure-generating capacities, reduced chronotropic reserve and impaired contractility. Conclusions: The study demonstrates for the first time impaired peak cardiac performance and cardiac functional reserve in asymptomatic CKD patients. The evidence of myocardial dysfunction in the absence of comorbid cardiac disease and diabetes warrants further evaluation of current pathophysiological concepts of cardiovascular disease in CKD.

Fast Exfoliation and Functionalisation of Two-Dimensional Crystalline Carbon Nitride by Framework Charging.

Two-dimensional (2D) layered graphitic carbon nitride (gCN) nanosheets offer intriguing electronic and chemical properties. However, the exfoliation and functionalisation of gCN for specific applications remain challenging. We report a scalable one-pot reductive method to produce solutions of single- and few-layer 2D gCN nanosheets with excellent stability in a high mass yield (35 %) from polytriazine imide. High-resolution imaging confirmed the intact crystalline structure and identified an AB stacking for gCN layers. The charge allows deliberate organic functionalisation of dissolved gCN, providing a general route to adjust their properties.

Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon Nanotubes.

Elemental phosphorus displays an impressive number of allotropes with highly diverse chemical and physical properties. White phosphorus has now been filled into single-wall carbon nanotubes (SWCNTs) from the liquid and thereby stabilized against the highly exothermic reaction with atmospheric oxygen. The encapsulated tetraphosphorus molecules were visualized with transmission electron microscopy, but found to convert readily into chain structures inside the SWCNT "nanoreactors". The energies of the possible chain structures were determined computationally, highlighting a delicate balance between the extent of polymerization and the SWCNT diameter. Experimentally, a single-stranded zig-zag chain of phosphorus atoms was observed, which is the lowest energy structure at small confinement diameters. These one-dimensional chains provide a glimpse into the very first steps of the transformation from white to red phosphorus.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Child and family health nurses working with families of preschool-aged children.

AIMS AND OBJECTIVES: To examine child and family health nurses' perceptions of and practices related to working with families of preschool-aged children about their child's behaviour. BACKGROUND: Emotional and behavioural problems in young children are of increasing concern. Child and family health nurses are well placed to support parents and provide education about behavioural concerns. DESIGN: A qualitative interpretive study informed by ethnography was used. METHODS: Forty-eight nurses participated in focus groups. Of these nurses, 11 participated in observations of clinical interactions with 23 mothers. Eight managers were interviewed. RESULTS: Three themes and two subthemes emerged from the data: Parents as deficit and nurse as expert; Parents have strengths and nurse as partner; Shaping practice - Time pressures and Wanting respect and to be valued. CONCLUSIONS: Child and family health nurses enjoy working with preschool-aged children; however, complex issues and tensions are evident. Nurses need support at all levels within the health service if they are to negotiate an environment of ongoing change and to be enabled to work in partnership with parents and families and thereby promote the emotional and behavioural development of preschool-aged children. RELEVANCE TO CLINICAL PRACTICE: The universal role of child and family health nurses provides unique opportunities to support parents about child behaviour concerns. Without appropriate support, nurses continue to work within an expert model that may alienate parents and families from using this service.

Flecainide induces a sustained countercurrent dependent effect on RyR2 in permeabilized WT ventricular myocytes but not in intact cells.

Background and purpose: While flecainide is now an accepted treatment for arrhythmias associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), its mechanism of action remains controversial. In studies on myocytes from CPVT mice, inhibition of proarrhythmic Ca2+ waves was initially attributed to a novel action on the type-2 ryanodine receptor (RyR2). However, subsequent work on wild type (WT) myocytes questioned the conclusion that flecainide has a direct action on RyR2. In the present study, the effects of flecainide were compared in intact and permeabilized WT myocytes. Experimental approach: Intracellular Ca2+ was measured using confocal microscopy in intact or saponin permeabilized adult rat ventricular myocytes (ARVM). In some experiments on permeabilized cells, flecainide was studied following partial inhibition of the sarcoplasmic reticulum (SR) counter-current. Key results: Flecainide induced sustained changes Ca2+ sparks and waves in permeabilized ARVM, which were comparable to those reported in intact or permeabilized myocytes from CPVT mice. However, a relatively high level of flecainide (25 µM) was required to induce these effects. Inhibition of the SR counter-current potentiated the effects of flecainide on SR Ca2+ waves. In intact field stimulated ARVM, prolonged exposure to 15 µM flecainide decreased wave frequency but RyR2 dependent effects on Ca2+ sparks were absent; higher drug concentrations blocked field stimulation, consistent with inhibition of Nav1.5. Conclusions and implications: In intact ARVM, the absence of effects on Ca2+ sparks suggests that the intracellular flecainide concentration was insufficient to influence RyR2. Wave inhibition in intact ARVM may reflect secondary effects of Nav1.5 inhibition. Potentiation of flecainide's action by counter-current inhibition can be explained if transient polarization of the SR membrane during SR Ca2+ release facilitates its action on RyR2.

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms.

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.

Extracting surface activation time from the optically recorded action potential in three-dimensional myocardium.

Optical mapping has become an indispensible tool for studying cardiac electrical activity. However, due to the three-dimensional nature of the optical signal, the optical upstroke is significantly longer than the electrical upstroke. This raises the issue of how to accurately determine the activation time on the epicardial surface. The purpose of this study was to establish a link between the optical upstroke and exact surface activation time using computer simulations, with subsequent validation by a combination of microelectrode recordings and optical mapping experiments. To simulate wave propagation and associated optical signals, we used a hybrid electro-optical model. We found that the time of the surface electrical activation (t(E)) within the accuracy of our simulations coincided with the maximal slope of the optical upstroke (t(F)*) for a broad range of optical attenuation lengths. This was not the case when the activation time was determined at 50% amplitude (t(F50)) of the optical upstroke. The validation experiments were conducted in isolated Langendorff-perfused rat hearts and coronary-perfused pig left ventricles stained with either di-4-ANEPPS or the near-infrared dye di-4-ANBDQBS. We found that t(F)* was a more accurate measure of t(E) than was t(F50) in all experimental settings tested (P = 0.0002). Using t(F)* instead of t(F50) produced the most significant improvement in measurements of the conduction anisotropy and the transmural conduction time in pig ventricles.

An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma.

Glioblastoma multiforme (GBM) is the most common and most aggressive form of intrinsic brain tumour. Despite standard treatment involving surgical resection, chemotherapy and radiotherapy this disease remains incurable with the majority of tumours recurring adjacent to the resection cavity. Consequently there is a clear need to improve local tumour control. Convection-enhanced delivery (CED) is a practical technique for administering chemotherapeutics directly into peritumoural brain. In this study, we have tested the hypothesis that carboplatin would be an appropriate chemotherapeutic agent to administer by CED into peritumoural brain to treat GBM. Within this study we have evaluated the relationships between carboplatin concentration, duration of exposure and tumour cell kill in vitro using GBM cell lines and the relationship between carboplatin concentration and clinical and histological evidence of toxicity in vivo. In addition, we have used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to evaluate the distribution properties of carboplatin following CED into rat brain and to determine the rate at which carboplatin is cleared from the brain. Finally, we have compared the distribution properties of carboplatin and the MRI contrast agent gadolinium-DTPA in pig brain. The results of these experiments confirm that carboplatin can be widely distributed by CED and that it remains in the brain for at least 24 h after infusion completion. Furthermore, carboplatin provokes a significant GBM cell kill at concentrations that are not toxic to normal brain. Finally, we provide evidence that gadolinium-DTPA coinfusion is a viable technique for visualising carboplatin distribution using T1-weighted MR imaging.